Mardiyyah/TAPT_data_V2_split · Datasets at Hugging Face

PMCID stringclasses 24 values	Title stringclasses 24 values	Sentences stringlengths 2 40.7k
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	In addition, we harmonized our skin fibroblast annotation with a previous classification (Supplementary Data Fig. 1b).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Overall, we provide a new framework for healthy human skin fibroblast annotation based on gene expression profiles (Fig. 1) and spatial location (Fig. 2) that integrates previous fibroblast descriptions in skin and across tissues.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Our findings of transcriptionally defined fibroblast subtypes in distinct microanatomical locations suggest a role for regional fibroblasts in supporting distinct niche functions.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We next sought to identify how fibroblast states change in diseased skin.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We used scPoli, a deep-learning model for integration and identification of novel cell states in single-cell transcriptome data (Methods) (Fig. 3a).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We mapped fibroblasts from skin diseases to our healthy/nonlesional F1–F5 fibroblast reference.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Out of 190,756 fibroblasts from diseased states, 121,167 diseased cells were confidently assigned existing F1–F5 cell labels (Extended Data Fig. 5a,b).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	The remaining 69,589 fibroblasts from the disease data were classified as uncertain (unlabeled) by scPoli (Fig. 3b).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Manual annotation based on differential gene expression (Supplementary Data Fig. 1c and Supplementary Table 3) and pathway analysis (Extended Data Fig. 5c) revealed two ‘disease-adapted’ and three ‘disease-specific’ fibroblast subtypes (Fig. 3b–f). ‘
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Disease-adapted’ fibroblasts resembled a healthy fibroblast subtype counterpart (Fig. 3e) and were expanded in disease settings (Fig. 3d).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	The first disease-adapted fibroblast subtype resembled F1: superficial fibroblasts in healthy skin (Fig. 3e).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	The F1-like disease population upregulated genes suggestive of regenerative function (CRABP1, CYP26B1 and WNT5A).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	CRABP1 and CYP26B1 are markers of superficial/upper wound fibroblasts in mice, which are thought to be the source of wound-induced hair follicle neogenesis, and involved in retinoic acid degradation.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	CRABP1 fibroblasts are also associated with regeneration in reindeer skin and early-gestational human skin.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	The second disease-adapted fibroblast subtype resembled F3: FRC-like fibroblasts and upregulated CXCL9 and/or ADAMDEC1 (Fig. 3e).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	CXCL9 is a chemoattractant for CXCR3 cells and has been reported as an activation marker for FRCs in lymphoid tissues. ‘
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Disease-specific’ fibroblasts (F6: inflammatory myofibroblasts, F7: myofibroblasts and F8: fascia-like myofibroblasts) did not have a healthy skin fibroblast counterpart and highly expressed a myofibroblast gene signature.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	This myofibroblast signature included contractility (ACTA2), extracellular matrix (ECM) (COL3A1, COL5A1, COL8A1, POSTN and CTHRC1) and other myofibroblast-associated genes (LRRC15, SFRP4, ASPN, RUNX2 and SCX) (Fig. 3c,g and Extended Data Fig. 5d,e).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F6: inflammatory myofibroblasts additionally expressed immune-related genes such as interleukins (IL11 and IL24), chemokines (CXCL5, CXCL8, CXCL13 and CCL11) and matrix metalloproteinases that can remodel tissue to facilitate immune cell infiltration (MMP1) (Fig. 3c).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	JAK–STAT and hypoxic signaling genes were also elevated (Fig. 3h).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F7: myofibroblasts and F8: fascia-like myofibroblasts were distinguished by a higher expression of ECM and TGFβ signaling genes, as well as the mechanotransducer PIEZO2 (Fig. 3c,h).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F8: fascia-like myofibroblasts were distinguished by expression of F_Fascia-associated genes (Fig. 3c).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Overall, our results indicate that healthy fibroblasts can acquire a regenerative phenotype in F1: superficial fibroblasts (CRABP1CYP27B1), a distinct polarization in F3: FRC-like fibroblasts (CXCL9/ADAMDEC1) and potentially give rise to myofibroblast states (ACTA2COL8A1SFRP4) in diseased skin.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We next leveraged the diverse clinical profiles of skin diseases to assess whether fibroblast subtypes provide molecular insights into disease endotypes with respect to scarring.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We assigned the 23 skin diseases into three clinically determined risk of scarring groups: low scarring risk, moderate scarring risk, and established scarring/fibrosis (see Methods) (Fig. 4a).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We excluded neurofibroma from this analysis as it was the only case of benign neoplasia, consisting primarily of F5: Schwann-like and F2/3: perivascular fibroblasts (Extended Data Fig. 6a).Fig.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	4Fibroblast compositional signatures characterize the stroma of distinct skin diseases and scarring risk categories.a, Proportion of fibroblast populations by individual disease.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Labels overlying each bar indicate the disease category.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	b, Proportion of disease-adapted and disease-specific fibroblast subtypes by disease category (mean ± s.e.m.).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Scarring risk group was based on clinical profiles (Methods).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	c, Immunofluorescence of LRRC15 (green) and ADAM12 (magenta) showing myofibroblast populations only in inflamed hidradenitis suppurativa skin (right-most) (from two representative atopic dermatitis and hidradenitis suppurativa inflamed and noninflamed samples).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Scale bar, 100 µm.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	d, Xenium 5k data for lesional/inflamed atopic dermatitis skin, with cells colored by cell type.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	e, Xenium 5k data for cutaneous melanoma, with cells colored by cell type.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	f, Proportion of fibroblast populations by disease status for Xenium 5k data.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	g, Gene module scores for each disease-associated fibroblast subtype across diseases with row normalization (0–1).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	VE, vascular endothelium; SCLE, subacute cutaneous lupus erythematosus; DLE, discoid lupus erythematosus.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	a, Proportion of fibroblast populations by individual disease.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Labels overlying each bar indicate the disease category.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	b, Proportion of disease-adapted and disease-specific fibroblast subtypes by disease category (mean ± s.e.m.).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Scarring risk group was based on clinical profiles (Methods).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	c, Immunofluorescence of LRRC15 (green) and ADAM12 (magenta) showing myofibroblast populations only in inflamed hidradenitis suppurativa skin (right-most) (from two representative atopic dermatitis and hidradenitis suppurativa inflamed and noninflamed samples).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Scale bar, 100 µm.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	d, Xenium 5k data for lesional/inflamed atopic dermatitis skin, with cells colored by cell type.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	e, Xenium 5k data for cutaneous melanoma, with cells colored by cell type.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	f, Proportion of fibroblast populations by disease status for Xenium 5k data.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	g, Gene module scores for each disease-associated fibroblast subtype across diseases with row normalization (0–1).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	VE, vascular endothelium; SCLE, subacute cutaneous lupus erythematosus; DLE, discoid lupus erythematosus.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We identified distinct fibroblast compositions for each scarring risk category (Fig. 4b).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Low scarring risk diseases were characterized by a high prevalence of F1: superficial (CRABPCYP27B1) and F3: FRC-like fibroblasts (CXCL9/ADAMDEC1) (Fig. 4b), without notable F6–F8 myofibroblast populations.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	This finding agrees with the regenerative-associated gene profile of disease-associated F1: superficial fibroblasts and a role for F3: FRC-like fibroblasts in maintaining immune niches.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Diseases with scarring risk were characterized by a uniquely high prevalence of F6: inflammatory myofibroblasts, which was not observed in low scarring risk or established fibrosis (Fig. 4b).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F7: myofibroblasts were observed at a similar prevalence in diseases with scarring risk and established fibrosis.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	These data point toward F6: inflammatory myofibroblast as a population influencing scarring risk, but which are largely absent in established fibrosis.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F8: fascia-like myofibroblasts were also elevated in established fibrosis but were predominantly observed in Dupuytren contracture, a fibroproliferative disease of the palmar fascia (Fig. 4a).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We used two further approaches to demonstrate the role for distinct fibroblast subtypes predicting scarring risk.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	First, we trained a random forest classifier and identified that F6: inflammatory myofibroblasts and F7: myofibroblasts were the most important fibroblast subtypes for predicting scarring risk category (Extended Data Fig. 6b).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Second, we profiled a well-recognized myofibroblast marker (LRRC15) at the protein level.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	LRRC15 was evident in inflammation with scarring risk (inflamed hidradenitis suppurativa skin) but not in noninflamed skin or inflamed skin without scarring risk (atopic dermatitis skin) (Fig. 4c).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Having established that disease-associated fibroblasts are enriched in distinct scarring categories, we next used spatial transcriptomics to validate these fibroblast populations in distinct scarring risk stroma (Fig. 4d–f and Supplementary Fig. 3).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	In keeping with scRNA-seq data (Fig. 4a), F3: FRC-like fibroblasts were expanded in inflamed atopic dermatitis skin (low risk), without major myofibroblasts (Fig. 4d,f and Extended Data Fig. 6c).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We localized the F3: FRC-like population to the superficial perivascular immune niche (Fig. 4d), which we further validated using 10x Visium data (Extended Data Fig. 6d–f).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	In melanoma (scarring risk), aside from F1, the entire stroma comprised F6: inflammatory myofibroblasts and F7: myofibroblasts (Fig. 4e,f and Extended Data Fig. 6g).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F7: myofibroblasts showed a matrix-producing phenotype (COL1A1, COL3A1 and POSTN) that characterizes myofibroblastic cancer-associated fibroblasts (CAFs) (myoCAFs).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F6: inflammatory myofibroblasts demonstrated high expression of inflammatory CAF (iCAF) marker genes (MMP1, MMP3, CXCL8 and IL24), which was observed in both cancer and inflammatory diseases with scarring risk (Extended Data Fig. 6h,i).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Finally, to complement our analysis of fibroblast proportions by disease, we assessed transcriptomic variability of disease-associated fibroblast subtypes by calculating gene module scores for each disease using defined marker genes to define transcriptomic variability across different disease conditions (Fig. 4g and Methods).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	The F6: inflammatory myofibroblast signature score was highest in hidradenitis suppurativa, acne and keratinocytic skin cancers.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Overall, our findings support distinct stromal composition in skin diseases associated with differential scarring risk.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F6: inflammatory myofibroblasts were observed in diseases with scarring risk but relatively infrequently observed in established fibrosis, raising the possibility that they may be an intermediate differentiation state toward F7: myofibroblasts.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	The differentiation process of healthy fibroblasts into myofibroblasts remains poorly understood in human tissues despite its clinical relevance.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Fibroblasts are tissue resident, and thus intermediate states of myofibroblast differentiation are likely to be captured in the molecular snapshots of skin diseases analyzed.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We therefore performed trajectory analysis of fibroblasts in diseased skin to gain further insights into myofibroblast differentiation, before utilizing time-resolved human wound data as a validation of dynamic changes in stromal composition.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We first included all fibroblast subtypes in a partition-based graph abstraction (PAGA) analysis (Extended Data Fig. 7a), and then focused further analyses on fibroblast populations found across diseases on hair-bearing and hairless skin (Methods).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	F7: myofibroblasts were a terminally differentiated myofibroblast state (Fig. 5a–c), consistent with their presence in established fibrosis.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	We observed two potential sources for F7: myofibroblasts in skin across analyses (Fig. 5b,c and Extended Data Fig. 7b).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	One trajectory arose directly from the F2: universal lineage.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	A second trajectory originated from F1: superficial fibroblasts, transitioning to F7: myofibroblasts via an intermediate F6: inflammatory myofibroblast state (Fig. 5a–c and Extended Data Fig. 7b).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	These two inferred trajectories are consistent with in vivo lineage tracing studies in mice.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Fig. 5Origin of skin disease-specific fibroblast subtypes.a–c, Velocity pseudotime (a), directed PAGA overlaid on UMAP (b) and velocity kernel from CellRank2 for lesional fibroblasts (c).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	For further details see Methods.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	d, UMAP visualization of fibroblast subtypes from human skin wounds data colored by cell type (left) and MKI67 (encodes Ki-67) expression (bottom right).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Proportions of fibroblast populations by time point (top right), where each bar represents a donor at a given time point.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	e, Schematic of predicted trajectories.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Dashed arrows indicate predictions with multiple lines of evidence.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Fibroblast populations are colored by the predominant scarring/fibrosis risk observed in an earlier analysis: green (prevalent in low-risk scarring stroma), orange (prevalent in scarring risk stroma and cancer), red (prevalent in established scarring/fibrotic disorders).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Gray boxes indicate signaling pathways identified in our gene expression/pathway analysis.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Schematic in e was partly created using BioRender.com.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	a–c, Velocity pseudotime (a), directed PAGA overlaid on UMAP (b) and velocity kernel from CellRank2 for lesional fibroblasts (c).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	For further details see Methods.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	d, UMAP visualization of fibroblast subtypes from human skin wounds data colored by cell type (left) and MKI67 (encodes Ki-67) expression (bottom right).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Proportions of fibroblast populations by time point (top right), where each bar represents a donor at a given time point.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	e, Schematic of predicted trajectories.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Dashed arrows indicate predictions with multiple lines of evidence.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Fibroblast populations are colored by the predominant scarring/fibrosis risk observed in an earlier analysis: green (prevalent in low-risk scarring stroma), orange (prevalent in scarring risk stroma and cancer), red (prevalent in established scarring/fibrotic disorders).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Gray boxes indicate signaling pathways identified in our gene expression/pathway analysis.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Schematic in e was partly created using BioRender.com.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	To investigate these predicted trajectories in real time, we leveraged a human skin wound dataset of 58,823 cells (Methods).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	Skin tissue had been collected from healthy human volunteers at baseline (pre-wound) and subsequently from healing wounds.
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	At baseline, myofibroblasts were not present, but on day 1 post-wounding, a small number of F6: inflammatory myofibroblasts were observed (Fig. 5d and Extended Data Fig. 7c).
PMC12479362	A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.	By day 7, F6: inflammatory myofibroblasts were the predominant population.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

In addition, we harmonized our skin fibroblast annotation with a previous classification (Supplementary Data Fig. 1b).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Overall, we provide a new framework for healthy human skin fibroblast annotation based on gene expression profiles (Fig. 1) and spatial location (Fig. 2) that integrates previous fibroblast descriptions in skin and across tissues.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Our findings of transcriptionally defined fibroblast subtypes in distinct microanatomical locations suggest a role for regional fibroblasts in supporting distinct niche functions.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We next sought to identify how fibroblast states change in diseased skin.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We used scPoli, a deep-learning model for integration and identification of novel cell states in single-cell transcriptome data (Methods) (Fig. 3a).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We mapped fibroblasts from skin diseases to our healthy/nonlesional F1–F5 fibroblast reference.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Out of 190,756 fibroblasts from diseased states, 121,167 diseased cells were confidently assigned existing F1–F5 cell labels (Extended Data Fig. 5a,b).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

The remaining 69,589 fibroblasts from the disease data were classified as uncertain (unlabeled) by scPoli (Fig. 3b).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Manual annotation based on differential gene expression (Supplementary Data Fig. 1c and Supplementary Table 3) and pathway analysis (Extended Data Fig. 5c) revealed two ‘disease-adapted’ and three ‘disease-specific’ fibroblast subtypes (Fig. 3b–f). ‘

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Disease-adapted’ fibroblasts resembled a healthy fibroblast subtype counterpart (Fig. 3e) and were expanded in disease settings (Fig. 3d).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

The first disease-adapted fibroblast subtype resembled F1: superficial fibroblasts in healthy skin (Fig. 3e).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

The F1-like disease population upregulated genes suggestive of regenerative function (CRABP1, CYP26B1 and WNT5A).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

CRABP1 and CYP26B1 are markers of superficial/upper wound fibroblasts in mice, which are thought to be the source of wound-induced hair follicle neogenesis, and involved in retinoic acid degradation.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

CRABP1 fibroblasts are also associated with regeneration in reindeer skin and early-gestational human skin.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

The second disease-adapted fibroblast subtype resembled F3: FRC-like fibroblasts and upregulated CXCL9 and/or ADAMDEC1 (Fig. 3e).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

CXCL9 is a chemoattractant for CXCR3 cells and has been reported as an activation marker for FRCs in lymphoid tissues. ‘

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Disease-specific’ fibroblasts (F6: inflammatory myofibroblasts, F7: myofibroblasts and F8: fascia-like myofibroblasts) did not have a healthy skin fibroblast counterpart and highly expressed a myofibroblast gene signature.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

This myofibroblast signature included contractility (ACTA2), extracellular matrix (ECM) (COL3A1, COL5A1, COL8A1, POSTN and CTHRC1) and other myofibroblast-associated genes (LRRC15, SFRP4, ASPN, RUNX2 and SCX) (Fig. 3c,g and Extended Data Fig. 5d,e).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F6: inflammatory myofibroblasts additionally expressed immune-related genes such as interleukins (IL11 and IL24), chemokines (CXCL5, CXCL8, CXCL13 and CCL11) and matrix metalloproteinases that can remodel tissue to facilitate immune cell infiltration (MMP1) (Fig. 3c).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

JAK–STAT and hypoxic signaling genes were also elevated (Fig. 3h).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F7: myofibroblasts and F8: fascia-like myofibroblasts were distinguished by a higher expression of ECM and TGFβ signaling genes, as well as the mechanotransducer PIEZO2 (Fig. 3c,h).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F8: fascia-like myofibroblasts were distinguished by expression of F_Fascia-associated genes (Fig. 3c).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Overall, our results indicate that healthy fibroblasts can acquire a regenerative phenotype in F1: superficial fibroblasts (CRABP1CYP27B1), a distinct polarization in F3: FRC-like fibroblasts (CXCL9/ADAMDEC1) and potentially give rise to myofibroblast states (ACTA2COL8A1SFRP4) in diseased skin.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We next leveraged the diverse clinical profiles of skin diseases to assess whether fibroblast subtypes provide molecular insights into disease endotypes with respect to scarring.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We assigned the 23 skin diseases into three clinically determined risk of scarring groups: low scarring risk, moderate scarring risk, and established scarring/fibrosis (see Methods) (Fig. 4a).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We excluded neurofibroma from this analysis as it was the only case of benign neoplasia, consisting primarily of F5: Schwann-like and F2/3: perivascular fibroblasts (Extended Data Fig. 6a).Fig.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

4Fibroblast compositional signatures characterize the stroma of distinct skin diseases and scarring risk categories.a, Proportion of fibroblast populations by individual disease.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Labels overlying each bar indicate the disease category.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

b, Proportion of disease-adapted and disease-specific fibroblast subtypes by disease category (mean ± s.e.m.).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Scarring risk group was based on clinical profiles (Methods).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

c, Immunofluorescence of LRRC15 (green) and ADAM12 (magenta) showing myofibroblast populations only in inflamed hidradenitis suppurativa skin (right-most) (from two representative atopic dermatitis and hidradenitis suppurativa inflamed and noninflamed samples).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Scale bar, 100 µm.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

d, Xenium 5k data for lesional/inflamed atopic dermatitis skin, with cells colored by cell type.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

e, Xenium 5k data for cutaneous melanoma, with cells colored by cell type.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

f, Proportion of fibroblast populations by disease status for Xenium 5k data.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

g, Gene module scores for each disease-associated fibroblast subtype across diseases with row normalization (0–1).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

VE, vascular endothelium; SCLE, subacute cutaneous lupus erythematosus; DLE, discoid lupus erythematosus.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

a, Proportion of fibroblast populations by individual disease.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Labels overlying each bar indicate the disease category.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

b, Proportion of disease-adapted and disease-specific fibroblast subtypes by disease category (mean ± s.e.m.).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Scarring risk group was based on clinical profiles (Methods).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

c, Immunofluorescence of LRRC15 (green) and ADAM12 (magenta) showing myofibroblast populations only in inflamed hidradenitis suppurativa skin (right-most) (from two representative atopic dermatitis and hidradenitis suppurativa inflamed and noninflamed samples).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Scale bar, 100 µm.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

d, Xenium 5k data for lesional/inflamed atopic dermatitis skin, with cells colored by cell type.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

e, Xenium 5k data for cutaneous melanoma, with cells colored by cell type.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

f, Proportion of fibroblast populations by disease status for Xenium 5k data.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

g, Gene module scores for each disease-associated fibroblast subtype across diseases with row normalization (0–1).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

VE, vascular endothelium; SCLE, subacute cutaneous lupus erythematosus; DLE, discoid lupus erythematosus.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We identified distinct fibroblast compositions for each scarring risk category (Fig. 4b).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Low scarring risk diseases were characterized by a high prevalence of F1: superficial (CRABPCYP27B1) and F3: FRC-like fibroblasts (CXCL9/ADAMDEC1) (Fig. 4b), without notable F6–F8 myofibroblast populations.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

This finding agrees with the regenerative-associated gene profile of disease-associated F1: superficial fibroblasts and a role for F3: FRC-like fibroblasts in maintaining immune niches.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Diseases with scarring risk were characterized by a uniquely high prevalence of F6: inflammatory myofibroblasts, which was not observed in low scarring risk or established fibrosis (Fig. 4b).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F7: myofibroblasts were observed at a similar prevalence in diseases with scarring risk and established fibrosis.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

These data point toward F6: inflammatory myofibroblast as a population influencing scarring risk, but which are largely absent in established fibrosis.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F8: fascia-like myofibroblasts were also elevated in established fibrosis but were predominantly observed in Dupuytren contracture, a fibroproliferative disease of the palmar fascia (Fig. 4a).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We used two further approaches to demonstrate the role for distinct fibroblast subtypes predicting scarring risk.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

First, we trained a random forest classifier and identified that F6: inflammatory myofibroblasts and F7: myofibroblasts were the most important fibroblast subtypes for predicting scarring risk category (Extended Data Fig. 6b).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Second, we profiled a well-recognized myofibroblast marker (LRRC15) at the protein level.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

LRRC15 was evident in inflammation with scarring risk (inflamed hidradenitis suppurativa skin) but not in noninflamed skin or inflamed skin without scarring risk (atopic dermatitis skin) (Fig. 4c).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Having established that disease-associated fibroblasts are enriched in distinct scarring categories, we next used spatial transcriptomics to validate these fibroblast populations in distinct scarring risk stroma (Fig. 4d–f and Supplementary Fig. 3).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

In keeping with scRNA-seq data (Fig. 4a), F3: FRC-like fibroblasts were expanded in inflamed atopic dermatitis skin (low risk), without major myofibroblasts (Fig. 4d,f and Extended Data Fig. 6c).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We localized the F3: FRC-like population to the superficial perivascular immune niche (Fig. 4d), which we further validated using 10x Visium data (Extended Data Fig. 6d–f).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

In melanoma (scarring risk), aside from F1, the entire stroma comprised F6: inflammatory myofibroblasts and F7: myofibroblasts (Fig. 4e,f and Extended Data Fig. 6g).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F7: myofibroblasts showed a matrix-producing phenotype (COL1A1, COL3A1 and POSTN) that characterizes myofibroblastic cancer-associated fibroblasts (CAFs) (myoCAFs).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F6: inflammatory myofibroblasts demonstrated high expression of inflammatory CAF (iCAF) marker genes (MMP1, MMP3, CXCL8 and IL24), which was observed in both cancer and inflammatory diseases with scarring risk (Extended Data Fig. 6h,i).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Finally, to complement our analysis of fibroblast proportions by disease, we assessed transcriptomic variability of disease-associated fibroblast subtypes by calculating gene module scores for each disease using defined marker genes to define transcriptomic variability across different disease conditions (Fig. 4g and Methods).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

The F6: inflammatory myofibroblast signature score was highest in hidradenitis suppurativa, acne and keratinocytic skin cancers.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Overall, our findings support distinct stromal composition in skin diseases associated with differential scarring risk.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F6: inflammatory myofibroblasts were observed in diseases with scarring risk but relatively infrequently observed in established fibrosis, raising the possibility that they may be an intermediate differentiation state toward F7: myofibroblasts.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

The differentiation process of healthy fibroblasts into myofibroblasts remains poorly understood in human tissues despite its clinical relevance.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Fibroblasts are tissue resident, and thus intermediate states of myofibroblast differentiation are likely to be captured in the molecular snapshots of skin diseases analyzed.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We therefore performed trajectory analysis of fibroblasts in diseased skin to gain further insights into myofibroblast differentiation, before utilizing time-resolved human wound data as a validation of dynamic changes in stromal composition.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We first included all fibroblast subtypes in a partition-based graph abstraction (PAGA) analysis (Extended Data Fig. 7a), and then focused further analyses on fibroblast populations found across diseases on hair-bearing and hairless skin (Methods).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

F7: myofibroblasts were a terminally differentiated myofibroblast state (Fig. 5a–c), consistent with their presence in established fibrosis.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

We observed two potential sources for F7: myofibroblasts in skin across analyses (Fig. 5b,c and Extended Data Fig. 7b).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

One trajectory arose directly from the F2: universal lineage.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

A second trajectory originated from F1: superficial fibroblasts, transitioning to F7: myofibroblasts via an intermediate F6: inflammatory myofibroblast state (Fig. 5a–c and Extended Data Fig. 7b).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

These two inferred trajectories are consistent with in vivo lineage tracing studies in mice.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Fig. 5Origin of skin disease-specific fibroblast subtypes.a–c, Velocity pseudotime (a), directed PAGA overlaid on UMAP (b) and velocity kernel from CellRank2 for lesional fibroblasts (c).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

For further details see Methods.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

d, UMAP visualization of fibroblast subtypes from human skin wounds data colored by cell type (left) and MKI67 (encodes Ki-67) expression (bottom right).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Proportions of fibroblast populations by time point (top right), where each bar represents a donor at a given time point.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

e, Schematic of predicted trajectories.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Dashed arrows indicate predictions with multiple lines of evidence.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Fibroblast populations are colored by the predominant scarring/fibrosis risk observed in an earlier analysis: green (prevalent in low-risk scarring stroma), orange (prevalent in scarring risk stroma and cancer), red (prevalent in established scarring/fibrotic disorders).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Gray boxes indicate signaling pathways identified in our gene expression/pathway analysis.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Schematic in e was partly created using BioRender.com.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

a–c, Velocity pseudotime (a), directed PAGA overlaid on UMAP (b) and velocity kernel from CellRank2 for lesional fibroblasts (c).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

For further details see Methods.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

d, UMAP visualization of fibroblast subtypes from human skin wounds data colored by cell type (left) and MKI67 (encodes Ki-67) expression (bottom right).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Proportions of fibroblast populations by time point (top right), where each bar represents a donor at a given time point.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

e, Schematic of predicted trajectories.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Dashed arrows indicate predictions with multiple lines of evidence.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Fibroblast populations are colored by the predominant scarring/fibrosis risk observed in an earlier analysis: green (prevalent in low-risk scarring stroma), orange (prevalent in scarring risk stroma and cancer), red (prevalent in established scarring/fibrotic disorders).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Gray boxes indicate signaling pathways identified in our gene expression/pathway analysis.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Schematic in e was partly created using BioRender.com.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

To investigate these predicted trajectories in real time, we leveraged a human skin wound dataset of 58,823 cells (Methods).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

Skin tissue had been collected from healthy human volunteers at baseline (pre-wound) and subsequently from healing wounds.

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

At baseline, myofibroblasts were not present, but on day 1 post-wounding, a small number of F6: inflammatory myofibroblasts were observed (Fig. 5d and Extended Data Fig. 7c).

PMC12479362

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.

By day 7, F6: inflammatory myofibroblasts were the predominant population.