Mardiyyah/TAPT_data_V2_split · Datasets at Hugging Face

PMCID stringclasses 24 values	Title stringclasses 24 values	Sentences stringlengths 2 40.7k
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.	We clustered cells at high resolution in each dataset and assigned cell annotations based on known marker gene expression and differential expression between clusters (Supplementary Table 2).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	To assist with label-aware integration, we established a three-level hierarchical cell-type annotation: class (level 1), type (level 2) and subtype (level 3) (Extended Data Fig. 1).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	To address batch effects and achieve a robust atlas integration, we assessed 12 different data-integration methods using single-cell integration benchmarking (Extended Data Fig. 1a–d), and selected scPoli to generate an integrated embedding of all organoid cells, enabling a cohesive representation of the diverse data (Fig. 1e and Extended Data Fig. 1e).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The integrated atlas was reannotated based on the most frequent cell type in each cluster, resulting in 5 cell classes at level 1, 48 cell types at level 2 and 51 cell subtypes at level 3 (Fig. 1f–h and Extended Data Fig. 1f).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Comparing annotations before and after integration with annotations in the original manuscripts showed a high consistency across most cell-type labels (Extended Data Fig. 2a–c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Inconsistencies were related to states on continuous differentiation trajectories and nomenclature granularity between publications (Supplementary Table 3).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Integration performance was unaffected by stem cell source, single-cell method or tissue type, but dataset origin substantially influenced integration outcomes (Extended Data Fig. 3 and Supplementary Table 4).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Pseudo-bulk analysis using both raw and scPoli embedding on all organoid single-cell datasets revealed stem cell source and tissue type as primary drivers of variance (Extended Data Fig. 4).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Overall, epithelial cells from different organs clustered together in the integrated atlas and clusters were composed of cells from different stem cell sources (Fig. 1e,i).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	However, we also identified cell types with contributions from multiple organoid models.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For example, goblet cells were found in both intestine (68.08%) and lung (31.84%), with a minor presence in other organs (0.08%).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Basal cells were observed in the lung (71.29%), salivary gland (16.28%), intestine (10.41%) and thyroid (1.32%) models (Fig. 1j).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	These results suggest the existence of cell types that exhibit partial or shared characteristics across different organ models, and also may indicate off-target cells in organoids.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We identified consistent markers for each integrated cell type across datasets and protocols, such as OLFM4 for stem cells and TP63 for basal cells (Fig. 1j and Supplementary Table 5).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We note instances in which cells derived from organoid models of a certain organ clustered with cells annotated as being from a different organ.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Given the difficulty in precisely controlling organoid development, especially PSC-derived organoids, off-target cells in organoids are a known issue.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	In addition, organoids derived from primary FSCs or ASCs could be contaminated because of handling or the adjacency of tissues during tissue acquisition, or cell states could be different from the tissue of origin because of stem cell plasticity.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Therefore, it is important to develop strategies to compare organoid cells with reference counterparts.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	To evaluate the fidelity of cell states observed in the human endoderm-derived organoid cell atlas (HEOCA), we obtained published scRNA-seq data on human endoderm-derived organs from adult (small and large intestine, lung, liver, pancreas, prostate, salivary gland) (Fig. 2a) and fetal (small and large intestine, lung, liver, pancreas, stomach, esophagus) (Fig. 2b) specimens.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	To assess on- and off-target cells in organoids, we projected organoid cells to the fetal and adult primary tissue atlases, and inferred the target tissue via label transfer (Fig. 2c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	PSC-derived organoids have a lower on-target percentage in both fetal and adult primary tissues compared with FSC- and ASC-derived organoids (Fig. 2c and Extended Data Fig. 5a–d).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Focusing on intestine and lung organoids, FSC- and ASC-derived intestine organoids demonstrated high on-target percentages, with an average of 91.12% in FSC-derived organoids and 98.14% in ASC-derived organoids (Fig. 2d).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	By contrast, PSC-derived organoids displayed a median on-target percentage of between 23.28% and 83.63% depending on fetal or adult reference atlas comparison; however, this is likely a low estimate because datasets from early organoid time points are difficult to assess using this reference comparison (Fig. 2c–e).Fig.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	2Mapping organoid cell types to a primary tissue reference atlas to assess organoid fidelity.a,b, UMAP representations of an integrated object comprising primary adult (a) and fetal (b) cell types and tissues are shown in the top right, as presented in the original publication.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	c, Bar plots showing the tissue proportion of the most similar adult (top) and fetal (bottom) tissue, sorted by organoid tissue and stem cell source.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The upper annotation bar indicates the organoid tissue and stem cell source, with tissue colors matching Fig. 1e and stem cell source colors matching Fig. 1i.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Matching tissue and organoid indicate on-target, whereas mismatched tissue and organoid indicate off-target.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Scaled color bars at the bottom of the bar plots represent the mean confidence of on-target and off-target cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Missing reference samples are depicted as a gray bar with a black line.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, Box plots reveal the percentage of on-target cells in intestine and lung organoid samples for adult (top) and fetal (bottom) cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, Similar to c, a subset of all intestine organoid epithelium cells projected to adult tissue is split by the source of stem cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	On- and off-target confidence is shown at the bottom of each bar plot, with three marker gene expressions in corresponding cell types shown at the top.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f, Box plots illustrate the highest similarity of all cell types in the corresponding primary adult and fetal tissues for each organoid sample, sorted as shown in c. g, UMAPs for primary adult (left) and fetal (right) tissues demonstrate the maximum similarity of all organoids in the comprehensive cross-tissue organoid atlas.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	h, Box plots show the maximum similarity of each adult (left) and fetal (right) cell type in different tissues.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	i, Box plots present the median similarity to primary adult (left) and fetal (right) cell types among different sources of stem cell organoids.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For plots in d, f, h and i, P values are from two-tailed Mann–Whitney U-tests.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	In box plots, the center represents the median; bounds show the 25% and 75% percentiles; and whiskers indicate values within 1.5× the interquartile range.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	EEC, enteroendocrine cell; NK, natural killer; PP, pancreatic polypeptide; TA, transit-amplifying.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	a,b, UMAP representations of an integrated object comprising primary adult (a) and fetal (b) cell types and tissues are shown in the top right, as presented in the original publication.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	c, Bar plots showing the tissue proportion of the most similar adult (top) and fetal (bottom) tissue, sorted by organoid tissue and stem cell source.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The upper annotation bar indicates the organoid tissue and stem cell source, with tissue colors matching Fig. 1e and stem cell source colors matching Fig. 1i.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Matching tissue and organoid indicate on-target, whereas mismatched tissue and organoid indicate off-target.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Scaled color bars at the bottom of the bar plots represent the mean confidence of on-target and off-target cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Missing reference samples are depicted as a gray bar with a black line.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, Box plots reveal the percentage of on-target cells in intestine and lung organoid samples for adult (top) and fetal (bottom) cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, Similar to c, a subset of all intestine organoid epithelium cells projected to adult tissue is split by the source of stem cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	On- and off-target confidence is shown at the bottom of each bar plot, with three marker gene expressions in corresponding cell types shown at the top.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f, Box plots illustrate the highest similarity of all cell types in the corresponding primary adult and fetal tissues for each organoid sample, sorted as shown in c. g, UMAPs for primary adult (left) and fetal (right) tissues demonstrate the maximum similarity of all organoids in the comprehensive cross-tissue organoid atlas.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	h, Box plots show the maximum similarity of each adult (left) and fetal (right) cell type in different tissues.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	i, Box plots present the median similarity to primary adult (left) and fetal (right) cell types among different sources of stem cell organoids.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For plots in d, f, h and i, P values are from two-tailed Mann–Whitney U-tests.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	In box plots, the center represents the median; bounds show the 25% and 75% percentiles; and whiskers indicate values within 1.5× the interquartile range.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	EEC, enteroendocrine cell; NK, natural killer; PP, pancreatic polypeptide; TA, transit-amplifying.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We identified major cell types from each adult and fetal tissue (Fig. 2a,b), and compared organoid cell types and states with primary counterparts using neighborhood graph correlation.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We quantified the proportion of cell types in each organoid sample and compared the similarity of each cell type with counterparts in adult and fetal tissues (Fig. 2f–h and Extended Data Fig. 5a,b).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	ASC-derived organoids had the highest similarity to adult counterparts, whereas PSC-derived organoids were most similar to fetal counterparts, with FSC-derived organoid cell states showing an intermediate distribution (Fig. 2i).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Multiple regression analyses revealed that similarity to reference atlases was influenced by publication and stem cell source but not by scRNA-seq methods, total sample counts or total sample genes (Extended Data Fig. 5e,f).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	To explore organoid cell states of different stem cell origin, we focused on intestinal organoid models in which there is substantial coverage from PSC-, FSC- and ASC-derived organoid cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	This subset consisted of 98 samples from 23 different publications representing 353,140 single-cell transcriptomes (Fig. 3a, Extended Data Fig. 6a and Supplementary Table 1).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We reintegrated all cells and defined 5 cell types at level 1, 26 cell types at level 2 and 32 cell types at level 3 in the atlas (Fig. 3b,c and Extended Data Fig. 6b,c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	This integrated intestinal organoid atlas (HIOCA) covers epithelial states from the duodenum, ileum, colon and PSC-derived organoids, and contains a large fraction of mesenchymal cells, and minor populations of neural, endothelial and immune cell types (Fig. 3b,c and Extended Data Fig. 6d–f).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We subsetted and reintegrated stem cells and enterocytes, and found that cells from different sources or tissues clustered together and exhibited distinct gene expression profiles (Extended Data Fig. 6h,i).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We used the large collection of protocols to examine factors that influence cell-type proportion (Extended Data Fig. 6m–o).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For instance, tumor necrosis factor (TNF) and interleukin-22 (IL-22) are linked to more abundant microfold (M) and Paneth cells in ASC-derived organoids, respectively, and xenografted PSC-derived tissues harbor both Paneth and tuft cells, which are absent in early stage PSC-derived organoids.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Protocol evaluation suggests tailored approaches to enrich specific cell types or enhanced maturation (Extended Data Fig. 6o).Fig.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	3Human intestinal organoids from different stem cell origins generate developing and adult cell states.a, Analytical design of the intestine organoid subatlas and comparison with the primary reference tissue.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	b,c, UMAP of healthy intestinal organoid atlas colored by level 1 cell-type annotation, source of intestine tissues and source of stem cells (b) and level 2 cell-type annotation (c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, Dot plots showing intestinal marker gene expression across organoid cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	From top to bottom, the dot plots display level 1 cell markers, epithelial cell markers and mesenchymal cell markers.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, Analytical design of the intestine organoid subatlas and comparison with the primary reference tissue.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f,g, UMAP of the integrated intestine fetal and adult primary tissue single-cell object colored by adult sample or fetal sample age (f) and cell type (g).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	h, Projection of intestine organoid cells onto fetal and adult primary epithelial single-cell objects categorized by PSC-, transplant PSC- (tPSC), FSC- and ASC-derived organoid samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	i, Bar plot illustrating the predicted cell proportions of each organoid sample mapped to the primary tissue objects.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The samples are divided by PSC-, FSC- and ASC-derived organoid samples, with PSC-derived organoids further ordered by organoid age, and FSC- and ASC-derived organoids ordered by the percentage of stem cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	j, Box plot showing the predicted probability of cell mapping to adult samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The cell numbers range from 1 to 10,866, with samples containing fewer than 100 cells marked by an asterisk.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	k, Bar plots illustrating the predicted tissue (fetal in gray and adult in blue) proportions.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	From top to bottom are stem cells, precursor enterocytes and enterocytes.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	l, Box plot showing the adult enterocytes similarity of each organoid sample.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The order of organoid samples in j, k and l is consistent with that in i. Biological sample size is 163.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For the box plots in j and l, the center represents the median; bounds show the 25% and 75% percentiles; and whiskers indicate values within 1.5× the interquartile range.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, day; mLTo, mesenchymal lymphoid tissue organizer.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	a, Analytical design of the intestine organoid subatlas and comparison with the primary reference tissue.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	b,c, UMAP of healthy intestinal organoid atlas colored by level 1 cell-type annotation, source of intestine tissues and source of stem cells (b) and level 2 cell-type annotation (c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, Dot plots showing intestinal marker gene expression across organoid cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	From top to bottom, the dot plots display level 1 cell markers, epithelial cell markers and mesenchymal cell markers.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, Analytical design of the intestine organoid subatlas and comparison with the primary reference tissue.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f,g, UMAP of the integrated intestine fetal and adult primary tissue single-cell object colored by adult sample or fetal sample age (f) and cell type (g).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	h, Projection of intestine organoid cells onto fetal and adult primary epithelial single-cell objects categorized by PSC-, transplant PSC- (tPSC), FSC- and ASC-derived organoid samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	i, Bar plot illustrating the predicted cell proportions of each organoid sample mapped to the primary tissue objects.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The samples are divided by PSC-, FSC- and ASC-derived organoid samples, with PSC-derived organoids further ordered by organoid age, and FSC- and ASC-derived organoids ordered by the percentage of stem cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	j, Box plot showing the predicted probability of cell mapping to adult samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The cell numbers range from 1 to 10,866, with samples containing fewer than 100 cells marked by an asterisk.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	k, Bar plots illustrating the predicted tissue (fetal in gray and adult in blue) proportions.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	From top to bottom are stem cells, precursor enterocytes and enterocytes.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	l, Box plot showing the adult enterocytes similarity of each organoid sample.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The order of organoid samples in j, k and l is consistent with that in i. Biological sample size is 163.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For the box plots in j and l, the center represents the median; bounds show the 25% and 75% percentiles; and whiskers indicate values within 1.5× the interquartile range.

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.

We clustered cells at high resolution in each dataset and assigned cell annotations based on known marker gene expression and differential expression between clusters (Supplementary Table 2).

PMC12081310

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

To assist with label-aware integration, we established a three-level hierarchical cell-type annotation: class (level 1), type (level 2) and subtype (level 3) (Extended Data Fig. 1).

PMC12081310

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

To address batch effects and achieve a robust atlas integration, we assessed 12 different data-integration methods using single-cell integration benchmarking (Extended Data Fig. 1a–d), and selected scPoli to generate an integrated embedding of all organoid cells, enabling a cohesive representation of the diverse data (Fig. 1e and Extended Data Fig. 1e).

PMC12081310

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

The integrated atlas was reannotated based on the most frequent cell type in each cluster, resulting in 5 cell classes at level 1, 48 cell types at level 2 and 51 cell subtypes at level 3 (Fig. 1f–h and Extended Data Fig. 1f).

PMC12081310

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

Comparing annotations before and after integration with annotations in the original manuscripts showed a high consistency across most cell-type labels (Extended Data Fig. 2a–c).

PMC12081310

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

Inconsistencies were related to states on continuous differentiation trajectories and nomenclature granularity between publications (Supplementary Table 3).

PMC12081310

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

Integration performance was unaffected by stem cell source, single-cell method or tissue type, but dataset origin substantially influenced integration outcomes (Extended Data Fig. 3 and Supplementary Table 4).

PMC12081310

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

Pseudo-bulk analysis using both raw and scPoli embedding on all organoid single-cell datasets revealed stem cell source and tissue type as primary drivers of variance (Extended Data Fig. 4).

PMC12081310

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

Overall, epithelial cells from different organs clustered together in the integrated atlas and clusters were composed of cells from different stem cell sources (Fig. 1e,i).

PMC12081310

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

However, we also identified cell types with contributions from multiple organoid models.

PMC12081310

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

For example, goblet cells were found in both intestine (68.08%) and lung (31.84%), with a minor presence in other organs (0.08%).

PMC12081310

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

Basal cells were observed in the lung (71.29%), salivary gland (16.28%), intestine (10.41%) and thyroid (1.32%) models (Fig. 1j).

PMC12081310

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

These results suggest the existence of cell types that exhibit partial or shared characteristics across different organ models, and also may indicate off-target cells in organoids.

PMC12081310

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

We identified consistent markers for each integrated cell type across datasets and protocols, such as OLFM4 for stem cells and TP63 for basal cells (Fig. 1j and Supplementary Table 5).

PMC12081310

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

We note instances in which cells derived from organoid models of a certain organ clustered with cells annotated as being from a different organ.

PMC12081310

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

Given the difficulty in precisely controlling organoid development, especially PSC-derived organoids, off-target cells in organoids are a known issue.

PMC12081310

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

In addition, organoids derived from primary FSCs or ASCs could be contaminated because of handling or the adjacency of tissues during tissue acquisition, or cell states could be different from the tissue of origin because of stem cell plasticity.

PMC12081310

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

Therefore, it is important to develop strategies to compare organoid cells with reference counterparts.

PMC12081310

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

To evaluate the fidelity of cell states observed in the human endoderm-derived organoid cell atlas (HEOCA), we obtained published scRNA-seq data on human endoderm-derived organs from adult (small and large intestine, lung, liver, pancreas, prostate, salivary gland) (Fig. 2a) and fetal (small and large intestine, lung, liver, pancreas, stomach, esophagus) (Fig. 2b) specimens.

PMC12081310

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

To assess on- and off-target cells in organoids, we projected organoid cells to the fetal and adult primary tissue atlases, and inferred the target tissue via label transfer (Fig. 2c).

PMC12081310

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

PSC-derived organoids have a lower on-target percentage in both fetal and adult primary tissues compared with FSC- and ASC-derived organoids (Fig. 2c and Extended Data Fig. 5a–d).

PMC12081310

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

Focusing on intestine and lung organoids, FSC- and ASC-derived intestine organoids demonstrated high on-target percentages, with an average of 91.12% in FSC-derived organoids and 98.14% in ASC-derived organoids (Fig. 2d).

PMC12081310

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

By contrast, PSC-derived organoids displayed a median on-target percentage of between 23.28% and 83.63% depending on fetal or adult reference atlas comparison; however, this is likely a low estimate because datasets from early organoid time points are difficult to assess using this reference comparison (Fig. 2c–e).Fig.

PMC12081310

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

2Mapping organoid cell types to a primary tissue reference atlas to assess organoid fidelity.a,b, UMAP representations of an integrated object comprising primary adult (a) and fetal (b) cell types and tissues are shown in the top right, as presented in the original publication.

PMC12081310

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

c, Bar plots showing the tissue proportion of the most similar adult (top) and fetal (bottom) tissue, sorted by organoid tissue and stem cell source.

PMC12081310

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

The upper annotation bar indicates the organoid tissue and stem cell source, with tissue colors matching Fig. 1e and stem cell source colors matching Fig. 1i.

PMC12081310

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

Matching tissue and organoid indicate on-target, whereas mismatched tissue and organoid indicate off-target.

PMC12081310

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

Scaled color bars at the bottom of the bar plots represent the mean confidence of on-target and off-target cells.

PMC12081310

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

Missing reference samples are depicted as a gray bar with a black line.

PMC12081310

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

d, Box plots reveal the percentage of on-target cells in intestine and lung organoid samples for adult (top) and fetal (bottom) cells.

PMC12081310

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

e, Similar to c, a subset of all intestine organoid epithelium cells projected to adult tissue is split by the source of stem cells.

PMC12081310

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

On- and off-target confidence is shown at the bottom of each bar plot, with three marker gene expressions in corresponding cell types shown at the top.

PMC12081310

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

f, Box plots illustrate the highest similarity of all cell types in the corresponding primary adult and fetal tissues for each organoid sample, sorted as shown in c. g, UMAPs for primary adult (left) and fetal (right) tissues demonstrate the maximum similarity of all organoids in the comprehensive cross-tissue organoid atlas.

PMC12081310

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

h, Box plots show the maximum similarity of each adult (left) and fetal (right) cell type in different tissues.

PMC12081310

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

i, Box plots present the median similarity to primary adult (left) and fetal (right) cell types among different sources of stem cell organoids.

PMC12081310

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

For plots in d, f, h and i, P values are from two-tailed Mann–Whitney U-tests.

PMC12081310

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

In box plots, the center represents the median; bounds show the 25% and 75% percentiles; and whiskers indicate values within 1.5× the interquartile range.

PMC12081310

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

EEC, enteroendocrine cell; NK, natural killer; PP, pancreatic polypeptide; TA, transit-amplifying.

PMC12081310

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

a,b, UMAP representations of an integrated object comprising primary adult (a) and fetal (b) cell types and tissues are shown in the top right, as presented in the original publication.

PMC12081310

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

c, Bar plots showing the tissue proportion of the most similar adult (top) and fetal (bottom) tissue, sorted by organoid tissue and stem cell source.

PMC12081310

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

The upper annotation bar indicates the organoid tissue and stem cell source, with tissue colors matching Fig. 1e and stem cell source colors matching Fig. 1i.

PMC12081310

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

Matching tissue and organoid indicate on-target, whereas mismatched tissue and organoid indicate off-target.

PMC12081310

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

Scaled color bars at the bottom of the bar plots represent the mean confidence of on-target and off-target cells.

PMC12081310

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

Missing reference samples are depicted as a gray bar with a black line.

PMC12081310

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

d, Box plots reveal the percentage of on-target cells in intestine and lung organoid samples for adult (top) and fetal (bottom) cells.

PMC12081310

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

e, Similar to c, a subset of all intestine organoid epithelium cells projected to adult tissue is split by the source of stem cells.

PMC12081310

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

On- and off-target confidence is shown at the bottom of each bar plot, with three marker gene expressions in corresponding cell types shown at the top.

PMC12081310

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

f, Box plots illustrate the highest similarity of all cell types in the corresponding primary adult and fetal tissues for each organoid sample, sorted as shown in c. g, UMAPs for primary adult (left) and fetal (right) tissues demonstrate the maximum similarity of all organoids in the comprehensive cross-tissue organoid atlas.

PMC12081310

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

h, Box plots show the maximum similarity of each adult (left) and fetal (right) cell type in different tissues.

PMC12081310

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

i, Box plots present the median similarity to primary adult (left) and fetal (right) cell types among different sources of stem cell organoids.

PMC12081310

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

For plots in d, f, h and i, P values are from two-tailed Mann–Whitney U-tests.

PMC12081310

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

In box plots, the center represents the median; bounds show the 25% and 75% percentiles; and whiskers indicate values within 1.5× the interquartile range.

PMC12081310

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

EEC, enteroendocrine cell; NK, natural killer; PP, pancreatic polypeptide; TA, transit-amplifying.

PMC12081310

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

We identified major cell types from each adult and fetal tissue (Fig. 2a,b), and compared organoid cell types and states with primary counterparts using neighborhood graph correlation.

PMC12081310

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

We quantified the proportion of cell types in each organoid sample and compared the similarity of each cell type with counterparts in adult and fetal tissues (Fig. 2f–h and Extended Data Fig. 5a,b).

PMC12081310

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

ASC-derived organoids had the highest similarity to adult counterparts, whereas PSC-derived organoids were most similar to fetal counterparts, with FSC-derived organoid cell states showing an intermediate distribution (Fig. 2i).

PMC12081310

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

Multiple regression analyses revealed that similarity to reference atlases was influenced by publication and stem cell source but not by scRNA-seq methods, total sample counts or total sample genes (Extended Data Fig. 5e,f).

PMC12081310

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

To explore organoid cell states of different stem cell origin, we focused on intestinal organoid models in which there is substantial coverage from PSC-, FSC- and ASC-derived organoid cells.

PMC12081310

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

This subset consisted of 98 samples from 23 different publications representing 353,140 single-cell transcriptomes (Fig. 3a, Extended Data Fig. 6a and Supplementary Table 1).

PMC12081310

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

We reintegrated all cells and defined 5 cell types at level 1, 26 cell types at level 2 and 32 cell types at level 3 in the atlas (Fig. 3b,c and Extended Data Fig. 6b,c).

PMC12081310

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

This integrated intestinal organoid atlas (HIOCA) covers epithelial states from the duodenum, ileum, colon and PSC-derived organoids, and contains a large fraction of mesenchymal cells, and minor populations of neural, endothelial and immune cell types (Fig. 3b,c and Extended Data Fig. 6d–f).

PMC12081310

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

We subsetted and reintegrated stem cells and enterocytes, and found that cells from different sources or tissues clustered together and exhibited distinct gene expression profiles (Extended Data Fig. 6h,i).

PMC12081310

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

We used the large collection of protocols to examine factors that influence cell-type proportion (Extended Data Fig. 6m–o).

PMC12081310

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

For instance, tumor necrosis factor (TNF) and interleukin-22 (IL-22) are linked to more abundant microfold (M) and Paneth cells in ASC-derived organoids, respectively, and xenografted PSC-derived tissues harbor both Paneth and tuft cells, which are absent in early stage PSC-derived organoids.

PMC12081310

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

Protocol evaluation suggests tailored approaches to enrich specific cell types or enhanced maturation (Extended Data Fig. 6o).Fig.

PMC12081310

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

3Human intestinal organoids from different stem cell origins generate developing and adult cell states.a, Analytical design of the intestine organoid subatlas and comparison with the primary reference tissue.

PMC12081310

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

b,c, UMAP of healthy intestinal organoid atlas colored by level 1 cell-type annotation, source of intestine tissues and source of stem cells (b) and level 2 cell-type annotation (c).

PMC12081310

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

d, Dot plots showing intestinal marker gene expression across organoid cell types.

PMC12081310

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

From top to bottom, the dot plots display level 1 cell markers, epithelial cell markers and mesenchymal cell markers.

PMC12081310

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

e, Analytical design of the intestine organoid subatlas and comparison with the primary reference tissue.

PMC12081310

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

f,g, UMAP of the integrated intestine fetal and adult primary tissue single-cell object colored by adult sample or fetal sample age (f) and cell type (g).

PMC12081310

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

h, Projection of intestine organoid cells onto fetal and adult primary epithelial single-cell objects categorized by PSC-, transplant PSC- (tPSC), FSC- and ASC-derived organoid samples.

PMC12081310

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

i, Bar plot illustrating the predicted cell proportions of each organoid sample mapped to the primary tissue objects.

PMC12081310

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

The samples are divided by PSC-, FSC- and ASC-derived organoid samples, with PSC-derived organoids further ordered by organoid age, and FSC- and ASC-derived organoids ordered by the percentage of stem cells.

PMC12081310

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

j, Box plot showing the predicted probability of cell mapping to adult samples.

PMC12081310

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

The cell numbers range from 1 to 10,866, with samples containing fewer than 100 cells marked by an asterisk.

PMC12081310

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

k, Bar plots illustrating the predicted tissue (fetal in gray and adult in blue) proportions.

PMC12081310

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

From top to bottom are stem cells, precursor enterocytes and enterocytes.

PMC12081310

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

l, Box plot showing the adult enterocytes similarity of each organoid sample.

PMC12081310

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

The order of organoid samples in j, k and l is consistent with that in i. Biological sample size is 163.

PMC12081310

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

For the box plots in j and l, the center represents the median; bounds show the 25% and 75% percentiles; and whiskers indicate values within 1.5× the interquartile range.

PMC12081310

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

d, day; mLTo, mesenchymal lymphoid tissue organizer.

PMC12081310

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

a, Analytical design of the intestine organoid subatlas and comparison with the primary reference tissue.

PMC12081310

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

b,c, UMAP of healthy intestinal organoid atlas colored by level 1 cell-type annotation, source of intestine tissues and source of stem cells (b) and level 2 cell-type annotation (c).

PMC12081310

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

d, Dot plots showing intestinal marker gene expression across organoid cell types.

PMC12081310

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

From top to bottom, the dot plots display level 1 cell markers, epithelial cell markers and mesenchymal cell markers.

PMC12081310

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

e, Analytical design of the intestine organoid subatlas and comparison with the primary reference tissue.

PMC12081310

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

f,g, UMAP of the integrated intestine fetal and adult primary tissue single-cell object colored by adult sample or fetal sample age (f) and cell type (g).

PMC12081310

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

h, Projection of intestine organoid cells onto fetal and adult primary epithelial single-cell objects categorized by PSC-, transplant PSC- (tPSC), FSC- and ASC-derived organoid samples.

PMC12081310

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

i, Bar plot illustrating the predicted cell proportions of each organoid sample mapped to the primary tissue objects.

PMC12081310

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

The samples are divided by PSC-, FSC- and ASC-derived organoid samples, with PSC-derived organoids further ordered by organoid age, and FSC- and ASC-derived organoids ordered by the percentage of stem cells.

PMC12081310

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

j, Box plot showing the predicted probability of cell mapping to adult samples.

PMC12081310

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

The cell numbers range from 1 to 10,866, with samples containing fewer than 100 cells marked by an asterisk.

PMC12081310

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

k, Bar plots illustrating the predicted tissue (fetal in gray and adult in blue) proportions.

PMC12081310

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

From top to bottom are stem cells, precursor enterocytes and enterocytes.

PMC12081310

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

l, Box plot showing the adult enterocytes similarity of each organoid sample.

PMC12081310

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

The order of organoid samples in j, k and l is consistent with that in i. Biological sample size is 163.

PMC12081310

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

For the box plots in j and l, the center represents the median; bounds show the 25% and 75% percentiles; and whiskers indicate values within 1.5× the interquartile range.