Mardiyyah/TAPT_data_V2_split · Datasets at Hugging Face

PMCID stringclasses 24 values	Title stringclasses 24 values	Sentences stringlengths 2 40.7k
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	It uses a flexible prioritization scheme that allows ranking L-R pairs according to several properties, such as niche- and region-specific expression of the L-R pair, ligand activity, and level of database curation.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	This in contrast to the default NicheNet pipeline which prioritizes expressed L-R pairs solely based on ligand activity predictions.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	All analyses were conducted according to the Differential NicheNet tutorial (https://github.com/saeyslab/nichenetr/blob/master/vignettes/differential_nichenet.md).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	As input to the Differential NicheNet pipeline, we used the data after normalization via SCTransform and integration of scRNA-seq and snRNA-seq according to the Seurat procedure for integration (Stuart et al., 2019).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	For the mouse analyses, Differential NicheNet was first performed for the following 3 niche comparisons: 1) KCs versus central vein macs; 2) KCs versus capsule macs; 3) KCs versus LAMs.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Following sender cell types were considered for these niches: KC niche: periportal hepatocytes, periportal LSECs, and periportal stellate cells; Central vein mac niche: central vein ECs and central vein fibroblasts; Capsule mac niche: mesothelial cells and capsule fibroblasts; LAM niche: cholangiocytes and bile duct fibroblasts.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Because of the preferentially periportal localization of KCs in the mouse liver, we also included a ‘region specificity' factor in the Differential NicheNet prioritization framework.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	This was done to increase the ranking of ligands that are more strongly expressed in periportal than pericentral niche cells.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Periportal sender cells were determined after subclustering based on the following markers: Hal and Sds for hepatocytes; Mecom, Msr1, and Efnb2 for LSECs; Ngfr, Igfbp3, and Dach1 for stellate cells.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	In the heatmap (Figure S8G), we show the prioritization scores of the top 40 ligands (and their highest scoring receptor) in the KC niche (score averaged over the 3 analyses), and of all the non-KC niche L-R pairs with a prioritization score ≥ the score of the lowest scoring KC L-R pair of this top 40.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	For each L-R pair/niche combination, we only displayed the score of the sender cell with the highest score (e.g. for the Csf1-Csf1r interaction in the KC niche, the score is shown for the LSEC-KC interaction because that score was higher than for Stellate–KC and Hepatocyte–KC; in the LAM niche, the score of Csf1-Csf1r is shown for the bile duct fibroblast – LAM interaction and not for the cholangiocyte–LAM interaction, etc.).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Because of the strong concordance between the top-ranked L-R pairs in these 3 non-KC mac niches, it was decided to also conduct a subsequent analysis in which the KC niche is compared against all non-KC hepatic mac niches combined.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	For this final ‘KC versus all non-KC mac analysis’, KCs were compared to central vein macs, capsule macs, and LAMs together, with the same sender cell types as described here above (but now analyzed together).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	For the human analyses, Differential NicheNet was performed to compare the KC niche with the non-KC mac niches (similarly as the final analysis in mouse).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	For the KC niche, all hepatocytes, LSECs, and stellate cells were selected as sender cells; and KCs as receiver cells.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	For the non-KC mac niche, cholangiocytes, fibroblasts, and central vein ECs were considered as the sender cells; Mat.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	LAMs, Imm.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	LAMs, and Mac1s as the receiver cells (Figure 4H).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	To find KC-niche-specific L-R pairs that are conserved across mouse and human, the individual mouse and human prioritization scores were averaged to form a ‘conservation score’.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	The 40 ligands (and maximally 3 of their highest scoring receptors) with the highest conservation score were selected for further analysis (note: the L-R pair should be expressed by the same sender-receiver pair in both species).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	In the circos plot (Figure 6C; Gu et al., 2014), only a subset of these top L-R pairs is shown to keep the figure clearly interpretable.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Following ligands were not shown: ITGA9, SEMA6D, JAM3, ITGB1 (stellate cells); ITGA9, F8, CD274, HSP90B1 (LSECs); C5, F9, F2, FGA, TF, TTR, COL18A1, COL5A3, SERPINA1, SERPINC1 (hepatocytes).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	The depicted target genes are KC-specific in both mouse and human, and a top-predicted target according to the NicheNet ligand-target regulatory potential scores.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	NR1H3 was manually added as a NOTCH2 target based on recent studies (Bonnardel et al., 2019).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Resected human liver was fixed in 4% formalin for 24-48h and subsequently embedded in paraffin.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Samples were stored for 10-15 years at RT before analysis.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Sections of 6 μm thick were cut using a Microm HM360 and mounted on a polarized glass slide.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	These sections were deparaffinized in xylene and rehydrated in a graded ethanol series.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Antigen retrieval was performed by immersing the samples for 5 min in pH 8.3 TRIS-EDTA at 98°C.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Slides were then cooled to RT and washed in PBS.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Confocal staining was performed as described above.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	BM was isolated from the tibia and femur of mice by centrifugation.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Red blood cells were lysed and single cell suspensions were stained with antibodies for flow cytometry.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	BM monocytes were sorted as live CD45+ CD11b+ Ly6G- Ly6C+ CD115+ cells using a BD FACSAria III.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Monocytes were resuspended in DMEM/F12 media supplemented with 10% FCS, 30ng/ml CSF1, 2mM Glutamine and 100U/ml penicillin and streptomycin.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	150,000 monocytes were seeded in each well of an adherent 24-well plate pre-coated with bovine collagen type I and cultured overnight (37C, 5% CO2).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	The following day 0, 25 or 50ng/ml of ac-LDL was added.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Ac-LDL was kindly provided by Sophie Janssens, Ghent, Belgium who received the material from Wilfried Le Goff, Paris, France.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	14 hours later cells were harvested and live F4/80+ cells were FACS-purified in RLT plus buffer containing 1% β-mercaptoethanol.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	RNA isolation, cDNA synthesis and qPCR were performed as described above.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Bone marrow chimeras were generated as described previously (Scott et al., 2016).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Briefly, 6-12 week old Clec4f-Dtr mice (CD45.1) were anaesthetized by intraperitoneal administration of Ketamine (150 mg/kg) and Xylazine (10 mg/kg).
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Mice were lethally irradiated with 8 Gy, with the livers being protected with a 3-cm-thick lead cover.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Once recovered from the anesthesia, mice were reconstituted by intravenous administration of 5-10×10 BM cells from CD45.2 Acvrl1 or Fcgr1-CrexAcvrl1l mice.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	4 weeks after reconstitution mice were administrated a single dose of 500ng DT via intraperitoneal injection to deplete KCs.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Chimerism was assessed 7 or 13 days later by flow cytometry and compared with chimerism levels in blood Ly6C monocytes.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Clec4f-Dtr mice were administered 10mg/kg ALK1Fc, TGFβRIIFc or appropriate isotype controls (hIgG1 and mIgG2a; Acceleron Pharma) by intraperitoneal injection on days -1, 2, 3 and 5.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	On Day 0 mice were also administered a single dose of 500ng DT i.p.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	to deplete KCs.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Livers were harvested at day 7 to assess KC development.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	In all experiments, data are presented as mean ±SEM and/or individual data points are presented unless stated otherwise.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Statistical tests were selected based on appropriate assumptions with respect to data distribution and variance characteristics.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Details of the precise test used for each analysis can be found in the figure legends.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Statistical significance was defined as p<0.05.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Sample sizes were chosen according to standard guidelines.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	Number of animals/patients is indicated as ‘‘n’’.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	The investigators were not blinded to the group allocation, unless otherwise stated.
PMC8809252	Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.	The sc/snRNA-sequencing, CITE-seq FCS files and spatial transcriptomics datasets will be made available for visualization, analysis and download at www.livercellatlas.org.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Human pluripotent stem cells and tissue-resident fetal and adult stem cells can generate epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Here, we integrate single-cell transcriptomes from 218 samples covering organoids and other models of diverse endoderm-derived tissues to establish an initial version of a human endoderm-derived organoid cell atlas.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The integration includes nearly one million cells across diverse conditions, data sources and protocols.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We compare cell types and states between organoid models and harmonize cell annotations through mapping to primary tissue counterparts.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Focusing on the intestine and lung, we provide examples of mapping data from new protocols and show how the atlas can be used as a diverse cohort to assess perturbations and disease models.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The human endoderm-derived organoid cell atlas makes diverse datasets centrally available and will be valuable to assess fidelity, characterize perturbed and diseased states, and streamline protocol development.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	In vitro human biosystems that model complex aspects of human tissues in controlled conditions can be used as inroads into human-specific biology and disease, as well as accurate alternatives to animal models.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The term organoid is a current nomenclature to describe three-dimensional (3D) cell cultures derived from pluripotent, fetal or adult stem cells (PSCs, FSCs, ASCs) that recapitulate important aspects of cell composition, cytoarchitecture and functional properties of the tissue counterpart.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	However, variations in protocols, culture conditions and stem cell sources make it challenging to assess how well organoid-derived cell states and interactions reflect those in vivo.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	In addition, the lack of centralized datasets and inconsistent protocol reporting complicate comparisons across studies, making it difficult to evaluate organoid fidelity, identify off-target or missing cell types, and predict genetic drivers of differentiation.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Overcoming these obstacles could help to better understand how human cell types and states develop, as well as support opportunities for translational research.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Advances in technology have led to the growth of single-cell transcriptome datasets, both in terms of dataset size and quantity.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	This has prompted collaborations to create extensive reference atlases for adult and developing human organs.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Organoids offer the opportunity to deepen our understanding of health and disease, by providing avatars of diverse developmental stages, genetic variation and disease states that will complement primary tissue atlases.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	However, the scale of generating a comprehensive organoid atlas in individual research groups is currently impractical.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Therefore, the integration of datasets generated by the wider research community becomes crucial.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The endoderm contributes to the development of the epithelial lining of a variety of different organs including thyroid, esophagus, lung, pancreas, liver, biliary system, stomach, small intestine and colon.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Complex endodermal 3D organoids can be differentiated from IPSCs, FSCs and ASCs in media supplemented with growth factors that promote stem cell proliferation and differentiation, potentially enabling exploration of human ontogenetic processes of each tissue.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Here, we present an integrated single-cell transcriptomic atlas of human endoderm-derived organoids encompassing nine different tissues, combining newly generated data and data from 55 publications.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We applied the atlas as a diverse cohort to assess organoid protocols, perturbations and disease models.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	To create an endoderm-derived organoid cell atlas, we assembled single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing data from 54 published datasets and a newly generated dataset (45,281 cells, 11 samples, small and large intestine, stomach and liver organoids) (Fig. 1a and Supplementary Table 1).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Together, these datasets include samples from 218 experiments conducted on organoid models of 9 different organs (lung, liver, biliary system, stomach, pancreas, small and large intestine, prostate, salivary glands) (Fig. 1a,b).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Data were obtained using multiple sequencing protocols, including plate-based methods such as Smart-seq, CEL-seq and Sort-seq, as well as commercialized droplet-based methods (for example, 10x Genomics) (Fig. 1c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Based on availability, we incorporated organoid datasets that model healthy states primarily of human endoderm-derived tissues, with source material from PSCs (embryonic stem cells and induced PSCs), FSCs or ASCs (Fig. 1d).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Notably, we obtained data of each stem cell source from intestine, lung, liver and biliary system organoid models (Fig. 1b,d).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	In total, we collected 806,646 cells to be utilized for downstream integration and analysis (Fig. 1a–d).Fig.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	1Integrated transcriptome cell atlas of human endoderm-derived organoids.a, Schematic overview of the atlas integration and downstream analyses.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	b, Box plot of cell number in samples from all publications, with sample number indicated below.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The center represents the median; bounds indicate 25% and 75% percentiles; and whiskers show minimum and maximum values within 1.5 times the interquartile range.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	c,d, Bar plot showing the number of samples grouped by different single-cell sequencing methods (c) and by tissue and stem cell source organoid (d).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, UMAP of the organoid atlas colored by tissue.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f, Overview of level 1 and level 2 cell annotations and cell proportion.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	g–i, Organoid atlas by level 1 annotations (g), level 2 annotations (h) or by stem cell source (i).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	j, Heatmap showing marker gene expression for each level 2 cell type in the atlas.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Side stacked bar plots show proportions of cell types at level 1, stem cell source and tissue type annotations.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	a, Schematic overview of the atlas integration and downstream analyses.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	b, Box plot of cell number in samples from all publications, with sample number indicated below.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The center represents the median; bounds indicate 25% and 75% percentiles; and whiskers show minimum and maximum values within 1.5 times the interquartile range.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	c,d, Bar plot showing the number of samples grouped by different single-cell sequencing methods (c) and by tissue and stem cell source organoid (d).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, UMAP of the organoid atlas colored by tissue.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f, Overview of level 1 and level 2 cell annotations and cell proportion.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	g–i, Organoid atlas by level 1 annotations (g), level 2 annotations (h) or by stem cell source (i).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

It uses a flexible prioritization scheme that allows ranking L-R pairs according to several properties, such as niche- and region-specific expression of the L-R pair, ligand activity, and level of database curation.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

This in contrast to the default NicheNet pipeline which prioritizes expressed L-R pairs solely based on ligand activity predictions.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

All analyses were conducted according to the Differential NicheNet tutorial (https://github.com/saeyslab/nichenetr/blob/master/vignettes/differential_nichenet.md).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

As input to the Differential NicheNet pipeline, we used the data after normalization via SCTransform and integration of scRNA-seq and snRNA-seq according to the Seurat procedure for integration (Stuart et al., 2019).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

For the mouse analyses, Differential NicheNet was first performed for the following 3 niche comparisons: 1) KCs versus central vein macs; 2) KCs versus capsule macs; 3) KCs versus LAMs.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Following sender cell types were considered for these niches: KC niche: periportal hepatocytes, periportal LSECs, and periportal stellate cells; Central vein mac niche: central vein ECs and central vein fibroblasts; Capsule mac niche: mesothelial cells and capsule fibroblasts; LAM niche: cholangiocytes and bile duct fibroblasts.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Because of the preferentially periportal localization of KCs in the mouse liver, we also included a ‘region specificity' factor in the Differential NicheNet prioritization framework.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

This was done to increase the ranking of ligands that are more strongly expressed in periportal than pericentral niche cells.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Periportal sender cells were determined after subclustering based on the following markers: Hal and Sds for hepatocytes; Mecom, Msr1, and Efnb2 for LSECs; Ngfr, Igfbp3, and Dach1 for stellate cells.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

In the heatmap (Figure S8G), we show the prioritization scores of the top 40 ligands (and their highest scoring receptor) in the KC niche (score averaged over the 3 analyses), and of all the non-KC niche L-R pairs with a prioritization score ≥ the score of the lowest scoring KC L-R pair of this top 40.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

For each L-R pair/niche combination, we only displayed the score of the sender cell with the highest score (e.g. for the Csf1-Csf1r interaction in the KC niche, the score is shown for the LSEC-KC interaction because that score was higher than for Stellate–KC and Hepatocyte–KC; in the LAM niche, the score of Csf1-Csf1r is shown for the bile duct fibroblast – LAM interaction and not for the cholangiocyte–LAM interaction, etc.).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Because of the strong concordance between the top-ranked L-R pairs in these 3 non-KC mac niches, it was decided to also conduct a subsequent analysis in which the KC niche is compared against all non-KC hepatic mac niches combined.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

For this final ‘KC versus all non-KC mac analysis’, KCs were compared to central vein macs, capsule macs, and LAMs together, with the same sender cell types as described here above (but now analyzed together).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

For the human analyses, Differential NicheNet was performed to compare the KC niche with the non-KC mac niches (similarly as the final analysis in mouse).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

For the KC niche, all hepatocytes, LSECs, and stellate cells were selected as sender cells; and KCs as receiver cells.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

For the non-KC mac niche, cholangiocytes, fibroblasts, and central vein ECs were considered as the sender cells; Mat.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

LAMs, Imm.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

LAMs, and Mac1s as the receiver cells (Figure 4H).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

To find KC-niche-specific L-R pairs that are conserved across mouse and human, the individual mouse and human prioritization scores were averaged to form a ‘conservation score’.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The 40 ligands (and maximally 3 of their highest scoring receptors) with the highest conservation score were selected for further analysis (note: the L-R pair should be expressed by the same sender-receiver pair in both species).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

In the circos plot (Figure 6C; Gu et al., 2014), only a subset of these top L-R pairs is shown to keep the figure clearly interpretable.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Following ligands were not shown: ITGA9, SEMA6D, JAM3, ITGB1 (stellate cells); ITGA9, F8, CD274, HSP90B1 (LSECs); C5, F9, F2, FGA, TF, TTR, COL18A1, COL5A3, SERPINA1, SERPINC1 (hepatocytes).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The depicted target genes are KC-specific in both mouse and human, and a top-predicted target according to the NicheNet ligand-target regulatory potential scores.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

NR1H3 was manually added as a NOTCH2 target based on recent studies (Bonnardel et al., 2019).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Resected human liver was fixed in 4% formalin for 24-48h and subsequently embedded in paraffin.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Samples were stored for 10-15 years at RT before analysis.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Sections of 6 μm thick were cut using a Microm HM360 and mounted on a polarized glass slide.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

These sections were deparaffinized in xylene and rehydrated in a graded ethanol series.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Antigen retrieval was performed by immersing the samples for 5 min in pH 8.3 TRIS-EDTA at 98°C.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Slides were then cooled to RT and washed in PBS.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Confocal staining was performed as described above.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

BM was isolated from the tibia and femur of mice by centrifugation.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Red blood cells were lysed and single cell suspensions were stained with antibodies for flow cytometry.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

BM monocytes were sorted as live CD45+ CD11b+ Ly6G- Ly6C+ CD115+ cells using a BD FACSAria III.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Monocytes were resuspended in DMEM/F12 media supplemented with 10% FCS, 30ng/ml CSF1, 2mM Glutamine and 100U/ml penicillin and streptomycin.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

150,000 monocytes were seeded in each well of an adherent 24-well plate pre-coated with bovine collagen type I and cultured overnight (37C, 5% CO2).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The following day 0, 25 or 50ng/ml of ac-LDL was added.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Ac-LDL was kindly provided by Sophie Janssens, Ghent, Belgium who received the material from Wilfried Le Goff, Paris, France.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

14 hours later cells were harvested and live F4/80+ cells were FACS-purified in RLT plus buffer containing 1% β-mercaptoethanol.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

RNA isolation, cDNA synthesis and qPCR were performed as described above.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Bone marrow chimeras were generated as described previously (Scott et al., 2016).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Briefly, 6-12 week old Clec4f-Dtr mice (CD45.1) were anaesthetized by intraperitoneal administration of Ketamine (150 mg/kg) and Xylazine (10 mg/kg).

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Mice were lethally irradiated with 8 Gy, with the livers being protected with a 3-cm-thick lead cover.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Once recovered from the anesthesia, mice were reconstituted by intravenous administration of 5-10×10 BM cells from CD45.2 Acvrl1 or Fcgr1-CrexAcvrl1l mice.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

4 weeks after reconstitution mice were administrated a single dose of 500ng DT via intraperitoneal injection to deplete KCs.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Chimerism was assessed 7 or 13 days later by flow cytometry and compared with chimerism levels in blood Ly6C monocytes.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Clec4f-Dtr mice were administered 10mg/kg ALK1Fc, TGFβRIIFc or appropriate isotype controls (hIgG1 and mIgG2a; Acceleron Pharma) by intraperitoneal injection on days -1, 2, 3 and 5.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

On Day 0 mice were also administered a single dose of 500ng DT i.p.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

to deplete KCs.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Livers were harvested at day 7 to assess KC development.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

In all experiments, data are presented as mean ±SEM and/or individual data points are presented unless stated otherwise.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Statistical tests were selected based on appropriate assumptions with respect to data distribution and variance characteristics.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Details of the precise test used for each analysis can be found in the figure legends.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Statistical significance was defined as p<0.05.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Sample sizes were chosen according to standard guidelines.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Number of animals/patients is indicated as ‘‘n’’.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The investigators were not blinded to the group allocation, unless otherwise stated.

PMC8809252

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The sc/snRNA-sequencing, CITE-seq FCS files and spatial transcriptomics datasets will be made available for visualization, analysis and download at www.livercellatlas.org.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Human pluripotent stem cells and tissue-resident fetal and adult stem cells can generate epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Here, we integrate single-cell transcriptomes from 218 samples covering organoids and other models of diverse endoderm-derived tissues to establish an initial version of a human endoderm-derived organoid cell atlas.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

The integration includes nearly one million cells across diverse conditions, data sources and protocols.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

We compare cell types and states between organoid models and harmonize cell annotations through mapping to primary tissue counterparts.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Focusing on the intestine and lung, we provide examples of mapping data from new protocols and show how the atlas can be used as a diverse cohort to assess perturbations and disease models.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

The human endoderm-derived organoid cell atlas makes diverse datasets centrally available and will be valuable to assess fidelity, characterize perturbed and diseased states, and streamline protocol development.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

In vitro human biosystems that model complex aspects of human tissues in controlled conditions can be used as inroads into human-specific biology and disease, as well as accurate alternatives to animal models.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

The term organoid is a current nomenclature to describe three-dimensional (3D) cell cultures derived from pluripotent, fetal or adult stem cells (PSCs, FSCs, ASCs) that recapitulate important aspects of cell composition, cytoarchitecture and functional properties of the tissue counterpart.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

However, variations in protocols, culture conditions and stem cell sources make it challenging to assess how well organoid-derived cell states and interactions reflect those in vivo.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

In addition, the lack of centralized datasets and inconsistent protocol reporting complicate comparisons across studies, making it difficult to evaluate organoid fidelity, identify off-target or missing cell types, and predict genetic drivers of differentiation.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Overcoming these obstacles could help to better understand how human cell types and states develop, as well as support opportunities for translational research.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Advances in technology have led to the growth of single-cell transcriptome datasets, both in terms of dataset size and quantity.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

This has prompted collaborations to create extensive reference atlases for adult and developing human organs.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Organoids offer the opportunity to deepen our understanding of health and disease, by providing avatars of diverse developmental stages, genetic variation and disease states that will complement primary tissue atlases.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

However, the scale of generating a comprehensive organoid atlas in individual research groups is currently impractical.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Therefore, the integration of datasets generated by the wider research community becomes crucial.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

The endoderm contributes to the development of the epithelial lining of a variety of different organs including thyroid, esophagus, lung, pancreas, liver, biliary system, stomach, small intestine and colon.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Complex endodermal 3D organoids can be differentiated from IPSCs, FSCs and ASCs in media supplemented with growth factors that promote stem cell proliferation and differentiation, potentially enabling exploration of human ontogenetic processes of each tissue.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Here, we present an integrated single-cell transcriptomic atlas of human endoderm-derived organoids encompassing nine different tissues, combining newly generated data and data from 55 publications.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

We applied the atlas as a diverse cohort to assess organoid protocols, perturbations and disease models.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

To create an endoderm-derived organoid cell atlas, we assembled single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing data from 54 published datasets and a newly generated dataset (45,281 cells, 11 samples, small and large intestine, stomach and liver organoids) (Fig. 1a and Supplementary Table 1).

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Together, these datasets include samples from 218 experiments conducted on organoid models of 9 different organs (lung, liver, biliary system, stomach, pancreas, small and large intestine, prostate, salivary glands) (Fig. 1a,b).

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Data were obtained using multiple sequencing protocols, including plate-based methods such as Smart-seq, CEL-seq and Sort-seq, as well as commercialized droplet-based methods (for example, 10x Genomics) (Fig. 1c).

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Based on availability, we incorporated organoid datasets that model healthy states primarily of human endoderm-derived tissues, with source material from PSCs (embryonic stem cells and induced PSCs), FSCs or ASCs (Fig. 1d).

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Notably, we obtained data of each stem cell source from intestine, lung, liver and biliary system organoid models (Fig. 1b,d).

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

In total, we collected 806,646 cells to be utilized for downstream integration and analysis (Fig. 1a–d).Fig.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

1Integrated transcriptome cell atlas of human endoderm-derived organoids.a, Schematic overview of the atlas integration and downstream analyses.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

b, Box plot of cell number in samples from all publications, with sample number indicated below.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

The center represents the median; bounds indicate 25% and 75% percentiles; and whiskers show minimum and maximum values within 1.5 times the interquartile range.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

c,d, Bar plot showing the number of samples grouped by different single-cell sequencing methods (c) and by tissue and stem cell source organoid (d).

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

e, UMAP of the organoid atlas colored by tissue.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

f, Overview of level 1 and level 2 cell annotations and cell proportion.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

g–i, Organoid atlas by level 1 annotations (g), level 2 annotations (h) or by stem cell source (i).

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

j, Heatmap showing marker gene expression for each level 2 cell type in the atlas.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

Side stacked bar plots show proportions of cell types at level 1, stem cell source and tissue type annotations.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

a, Schematic overview of the atlas integration and downstream analyses.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

b, Box plot of cell number in samples from all publications, with sample number indicated below.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

The center represents the median; bounds indicate 25% and 75% percentiles; and whiskers show minimum and maximum values within 1.5 times the interquartile range.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

c,d, Bar plot showing the number of samples grouped by different single-cell sequencing methods (c) and by tissue and stem cell source organoid (d).

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

e, UMAP of the organoid atlas colored by tissue.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

f, Overview of level 1 and level 2 cell annotations and cell proportion.

PMC12081310

An integrated transcriptomic cell atlas of human endoderm-derived organoids.

g–i, Organoid atlas by level 1 annotations (g), level 2 annotations (h) or by stem cell source (i).