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.
|
e, Dotplot of expression of marker genes for adult skin F3: FRC-like fibroblasts and LTo-associated marker genes in diseased adult skin, by disease, for diseases with a minimum of 100 F3: FRC-like fibroblasts.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
DRESS, drug reaction with eosinophilia and systemic symptoms.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
f, Dotplot of expression of F3: FRC-like fibroblast marker genes in mouse steady-state cross-tissue atlas (Buechler et al.).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
g, Proportion of Ccl19 fibroblasts (labels from original study) in mouse in different healthy tissues (including mouse flank skin) and of F3: FRC-like fibroblasts in healthy human skin.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Illustrations in f and g were 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.
|
We next queried whether prenatal CCL19 fibroblasts were equivalent to LTo-like cells by jointly integrating human prenatal skin and intestinal data.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Notably, prenatal skin CCL19 cells and prenatal intestinal mesenchymal LTo cells clustered together (Fig. 8c).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Prenatal skin CCL19 cells expressed known mesenchymal LTo markers, including CCL21, CXCL13, MADCAM1, FDCSP and TNFSF11 (RANKL) (Fig. 8c), suggesting that prenatal skin CCL19 cells may give rise to adult skin F3: FRC-like cells in a manner analogous to intestinal LTo cells.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We next investigated the LTo gene program in adult skin F3: FRC-like fibroblasts.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
The LTo gene program (including CXCL13 and FDCSP) was not expressed in healthy adult skin but could be upregulated in specific skin diseases (Fig. 8d,e), particularly hidradenitis suppurativa.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Tertiary lymphoid structures (TLS), for which CXCL13 is an important chemokine, are not well recognized in adult human skin, but have recently been reported in hidradenitis suppurativa specifically, suggesting that the LTo gene program contributes to this process.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We next asked whether F3: FRC-like fibroblasts were unique to adult human skin, as LTo-like fibroblasts have not been reported in mouse embryonic skin.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Our comparative analysis showed that adult F3: FRC-like cells correspond to mouse Ccl19 fibroblasts (Fig. 8f).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Mouse Ccl19 fibroblasts were found predominantly in lymphoid organs (Extended Data Fig. 10a), but were also present in other tissues such as lung (Fig. 8g), whereas F3: FRC-like fibroblasts were relatively abundant in healthy human skin, the equivalent Ccl19 fibroblasts were notably rarer in healthy mouse skin (Fig. 8g).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
In summary, we suggest F3: FRC-like fibroblasts are enriched in human skin and not observed or absent in murine skin.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We harmonize skin fibroblast subtype nomenclature in health and disease, spatially resolve distinct fibroblast anatomical niches, and identify conserved fibroblast subtypes in human diseases affecting multiple tissues.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
FRCs are the paradigm of immunomodulatory fibroblasts, maintaining discrete immune structures and facilitating specific immune cell interactions in lymphoid organs, with increasing evidence that they are present across human tissues.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Our data suggest that F3: FRC-like fibroblasts are located in the superficial perivascular niche in human skin and have an analogous role to T zone reticular FRCs, mediating T-DC interactions.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
In keeping with previous murine studies, we find that F3: FRC-like fibroblasts show a uniquely high prevalence in human skin.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
This enrichment of F3: FRC-like fibroblasts in human skin would explain both the absence of fibroblasts in murine skin TLS-like structures and why the prominent perivascular infiltrate structures that characterize many human inflammatory skin diseases are not reported in mice.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Inflammatory myofibroblasts were recently reported in a large-scale integration of predominantly CAFs and have been independently described in IBD.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We identify that the same inflammatory myofibroblast phenotype (IL11MMP1CXCL8IL7R) can be observed in early human skin wounds, skin cancer and inflammatory skin diseases with scarring risk.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Consistent with the immune milieu in early wounds, acne and hidradenitis suppurativa, we suggest that these fibroblasts recruit immune cells such as neutrophils and monocytes.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Neutrophils are also reported to be recruited by inflammatory myofibroblasts in IBD.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Our study also suggests that F6: inflammatory myofibroblasts are an intermediate myofibroblast differentiation state in human skin, which agrees with recent work in mouse skin and lung.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Further work validating myofibroblast trajectories in human skin is needed as current trajectory inference methods are limited for predicting multiple cell states converging to a final phenotype, and lineage plasticity is likely in fibroblasts, with both tissue-specific and universal populations suggested to give rise to myofibroblasts.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Notably, skin could serve as an exemplar tissue to further investigate myofibroblast development in humans in vivo given the ability to sample tissue temporally with low morbidity.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
A limitation of our study is that we relied on the uncertainty mechanism incorporated in scPoli to identify disease-associated populations.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Our cross-tissue analysis using semi-supervised integration may underestimate tissue-specific differences between fibroblasts, and further investigation using methods such as contrastive analysis may be valuable.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
LTo-like cells in prenatal skin were rare and more definitive lineage tracing methods are required to understand prenatal to adult fibroblast transitions.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
In summary, our annotated skin fibroblast dataset of 357,276 cells provides a foundational resource for fibroblast transcriptomic states in health and across distinct disease categories in skin tissue.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Further comments on annotation can be made via the centralized community annotation platform (https://celltype.info/project/388).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Raw scRNA-seq data were downloaded and aligned using STARsolo (GRCh38-2020-A reference) unless already available in local storage.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We included publicly available data generated from fresh skin biopsies using the 10x Genomics Chromium platform.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We collected essential metadata (sample ID, dataset ID, site status, patient status, sex and anatomic location) as more extensive metadata are being collected as part of the Human Skin Cell Atlas.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
CellBender v.0.3 was used to correct for ambient messenger RNA.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
To remove low-quality cells, we included only cells with >200 genes, >1,000 and <300,000 total unique molecular identifiers and a mitochondrial gene percentage of <15%.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We calculated doublet scores using scrublet on a per sample basis using scrublet and removed cells with a doublet score of >0.3 (ref. ).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Integration of all cells was performed using scVI using raw counts.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
For feature (highly variable gene (HVG)) selection, we did not consider the following genes: mitochondrial genes; cell cycle genes, from https://github.com/haniffalab/skin_fibroblast_atlas/blob/main/misc/cc_genes.csv); hypoxic genes; and ribosomal genes.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We selected 6,000 HVGs as features, and batch-aware HVG selection was performed by setting the batch key to sample ID.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
In future analyses post-integration, all genes were considered.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
The following hyperparameters were used for the scVI model: number of layers: 2; number of latent dimensions: 30; gene likelihood: zero-inflated negative binomial distribution, and dispersion: gene-batch.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
An early stopping patience of five epochs was used.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
The batch key was ‘sampleID’ and no other covariates were passed to the model for correction.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We constructed a k-nearest neighbors (k-NN) graph (k = 30) using the scVI embedding and performed community detection (Leiden algorithm) with resolution 0.1 for the dataset with all skin cells.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Visualization in two dimensions was performed using UMAP with the initialized positions from PAGA implemented in scanpy.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We then selected the fibroblast cluster for further analysis based on canonical marker gene expression, including PDGFRA, DCN and LUM) (Extended Data Fig. 1a).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We did not include a distinct stress response cluster (MT2A, MT1M, MT1X, HSP90AA1, JUNB, GADD45B and IER3) as this population was not evident on Xenium analysis and thus likely related to cell dissociation.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
For a sensitivity analysis with additional cell types, we also selected Schwann and pericyte clusters.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We repeated integration using scVI for healthy and phenotypically normal (nonlesional) skin fibroblasts only.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We used the same workflow as above.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Visualization in two dimensions was performed using UMAP with positions initialized from PAGA.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We show gene expression values post-normalization.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Normalization is a two-step procedure involving depth normalization and variance stabilization.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We used the shifted logarithm with a scaling factor of 10,000 based on strong performance in a recent benchmarking paper.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
For each cluster, we calculated differentially expressed genes (DEGs) using the t-test with the scanpy rank_genes_groups function.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
The top DEGs for each population are shown in Supplementary Fig. 1a and Supplementary Table 2.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
For selecting marker genes to present for each population in Fig. 1c, we selected genes with the highest specificity of expression for that cluster from visualization.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We selected our nomenclature for fibroblasts based on our previous report of F1–F3 fibroblasts.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We refined the names based on spatial location and our in-depth characterization of cell states, including across tissues.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We renamed F1 as F1: superficial, F2 to F2: universal and F3 to F3: FRC-like.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
In this work, we defined novel fibroblast subtypes.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
F2/3 fibroblasts expressed select F2 (CD34 and PI16) and F3 markers (CXCL12, PLA2G2A and C7), but additionally expressed PPARG.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
F2/3 fibroblasts also showed a distinct location enriched in both superficial and deep dermal perivascular structures, compared to F2 (deep dermis but not around vasculature) and F3 (superficial perivascular regions) (Extended Data Fig. 4c).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We therefore named this population F2/F3: Perivascular.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We additionally identified novel F4 and F5 populations.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We grouped three subtypes as F4 based on transcriptomic (ASPN/COL11A1) and spatial similarity (localization around the hair follicle).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We grouped two subtypes as F5 based on shared expression of genes also expressed by Schwann cells, including SCN7A, FMO2 and OFLML2A, and spatial association with nerve structures.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We took two approaches to minimize the possibility of missing a rare distinct cluster.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
First, we repeated unsupervised clustering at a higher resolution and assessed whether any clusters showed distinct gene expression.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Second, we reviewed reported marker genes for fibroblast clusters in previously reported scRNA-seq data for human skin to identify if a novel distinct population has been reported.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Transcription factor activity inference was performed using decoupler, using the get_collectri (human) and run_ulm functions.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
This analysis was performed using the data subset of 6,000 HVGs.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Gene set enrichment analysis was implemented using GSEAPY.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We used the top 500 DEGs per fibroblast subtype and the GO_Biological_Process_2023 gene set.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
A cutoff statistical significance of 0.01 was used.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We generated new spot-based spatial transcriptomic data using the 10x Genomics Visium Spatial Gene Expression platform from frozen OCT-embedded human adult skin tissue (n = 1 lesional atopic dermatitis and n = 2 nonlesional atopic dermatitis).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
All research ethics committee and regulatory approvals were in place for the collection of research samples at Newcastle and for their storage at the Newcastle Dermatology Biobank (REC reference no. 19/NE/0004).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Skin samples were sectioned at 15-µm thickness and the optimal tissue permeabilization time was determined as 14 min.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
H&E images were taken using a Zeiss AxioImager with apotome microscope (Carl Zeiss Microscopy) and Brightfield imaging (Zeiss Axiocam 105 48-color camera module) at ×20 magnification.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
The ZEN blue edition v.3.1 (Carl Zeiss Microscopy) software was used to acquire the H&E images following z-plane and light balance adjustment and image tile stitching.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Spatial gene expression libraries were sequenced using an Illumina NovaSeq 6000 to achieve a minimum number of 50,000 read pairs per tissue covered spot.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
The 10x Genomics Visium data were mapped using Spaceranger v.1.3.0 using GRCh38-2020-A reference.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Visium provides whole transcriptome coverage over a 55-μm diameter spot area.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We therefore used the cell2location (v.0.1.3) to deconvolute the cell types predicted to be present in a given spot.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We constructed a reference signature using sample as batch_key.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We included our fibroblast atlas and other skin cell types from Reynolds et al.. Then we performed deconvolution with the following parameters: detection_alpha = 20,N_cells_per_location = 30 andmax_epochs 50_000.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Values of all other parameters were kept default.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Following the cell2location tutorial, we used 5% quantile of posterior distribution (q05_cell_abundance_w_sf) as predicted cell-type abundances.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Nonlesional (n = 2; one sample nonlesional pre-treatment, one sample nonlesional post-treatment) and lesional (n = 1; inflamed) atopic dermatitis human adult skin tissue was used to generate in situ gene expression data using the 10x Genomics Xenium in situ 5k-plex platform.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
All research ethics committees and regulatory approvals were in place for the collection and storage of research samples at St John’s Institute of Dermatology, Guy’s Hospital, London (REC reference no. EC00/128).
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
The 10x Genomics Xenium data were filtered to exclude cells with <10 genes per cell.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Integration of all cells was performed using scVI using raw counts.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
Batch-aware HVG selection was performed by setting the batch key to sample ID.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We selected 2,000 HVGs as features for the integration.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
As Xenium data are more sparse than scRNA data, we used a simpler encoder (number of layers: 1; number of latent dimensions: 10) than scRNA.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
The batch key was ‘sampleID’ and no other covariates were passed to the model for correction.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
For normalization, we again used the shifted log transformation for count normalization.
|
PMC12479362
|
A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.
|
We constructed a k-NN graph (k = 20, given the smaller dataset size) using the scVI embedding.
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.