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.	We found that DEGs identified from comparison with the HEOCA cohort were similar to the set identified through comparison with the isogenic control (Extended Data Fig. 9a,b).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	To assess the biological relevance of the identified states, we compared transcriptomes with counterpart epithelium in an atlas of inflammatory bowel disease (IBD) patient samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Interestingly, we found that the perturbation-induced DEGs were also differentially expressed between healthy individuals and patients with IBD (Fig. 6i, j).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	This finding confirms that these perturbations generate organoid cell states not prevalent in the atlas, that the integrated atlas can be used as a diverse cohort for perturbation assessment and that these perturbation states have relevance to primary counterparts.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Fig. 6Organoid perturbation and comparison with the HEOCA extends the cell state repertoire.a, Summary of the cytokines used to treat ileum organoids for viral response and inflammation.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The HEOCA provides a diverse cohort of cell types and states that can be used as a control for comparing perturbation conditions to reveal DEGs and under-represented cell states.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	b, UMAP of sample scRNA-seq data mapped to the HEOCA, colored by predicted level 2 cell types, from left to right: control, viral response and inflammation.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	c, Bar plot depicting the cell proportions of predicted level 2 cell types across control and cytokine treatment scRNA-seq data.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, UMAP of the integrated control and cytokine treatment samples, colored by sample, cell types and distance to HEOCA.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, Box plot comparing distance to HEOCA among control and treatment samples across different cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f, Scatter plot showing genes differentially expressed between cytokine treatment samples and the HEOCA cohorts.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	g, Dot plots displaying an example gene expression comparison of HEOCA and cytokine treatment samples across different cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	h, Heatmap illustrating the DEGs GO enrichment comparison among different cytokine treatments and HEOCA cohorts.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The P value was computed using Fisher’s exact test.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	i, Organoid perturbation expression signatures were compared for intestinal epithelial cell single-cell transcriptome data from patients with different IBDs.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Box plots show the distribution of mean expression of genes differentially expressed between inflammatory or viral response conditions (compared with the HEOCA control cohort), and the overlap of DEGs between both conditions.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	j, Distribution of mean gene expression across IBD conditions for representative genes induced in viral response and inflammatory conditions.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For box plots in e, i and j, P values are derived from two-tailed Mann–Whitney U-test. *
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	P < 0.05, P < 0.001, *P < 0.001).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	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.	Inflam, infammation.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	a, Summary of the cytokines used to treat ileum organoids for viral response and inflammation.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The HEOCA provides a diverse cohort of cell types and states that can be used as a control for comparing perturbation conditions to reveal DEGs and under-represented cell states.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	b, UMAP of sample scRNA-seq data mapped to the HEOCA, colored by predicted level 2 cell types, from left to right: control, viral response and inflammation.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	c, Bar plot depicting the cell proportions of predicted level 2 cell types across control and cytokine treatment scRNA-seq data.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, UMAP of the integrated control and cytokine treatment samples, colored by sample, cell types and distance to HEOCA.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, Box plot comparing distance to HEOCA among control and treatment samples across different cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f, Scatter plot showing genes differentially expressed between cytokine treatment samples and the HEOCA cohorts.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	g, Dot plots displaying an example gene expression comparison of HEOCA and cytokine treatment samples across different cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	h, Heatmap illustrating the DEGs GO enrichment comparison among different cytokine treatments and HEOCA cohorts.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	The P value was computed using Fisher’s exact test.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	i, Organoid perturbation expression signatures were compared for intestinal epithelial cell single-cell transcriptome data from patients with different IBDs.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Box plots show the distribution of mean expression of genes differentially expressed between inflammatory or viral response conditions (compared with the HEOCA control cohort), and the overlap of DEGs between both conditions.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	j, Distribution of mean gene expression across IBD conditions for representative genes induced in viral response and inflammatory conditions.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For box plots in e, i and j, P values are derived from two-tailed Mann–Whitney U-test. *
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	P < 0.05, P < 0.001, *P < 0.001).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	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.	Inflam, infammation.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We next assessed the utility of the integrated atlas to understand organoid models of disease.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Through comparison with the HEOCA we assess cell proportion, identify disease-associated states and perform differential expression analysis against the atlas data (Fig. 5a).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	We first explored colorectal cancer (CRC) using a dataset composed of CRC organoids from a patient resection and normal organoids from adjacent healthy tissue (Fig. 7a).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	HEOCA mapping analysis showed that CRC samples exhibited a lower percentage of mature colonocytes, and a higher proportion of stem cells (Fig. 7b,c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Interestingly, we also observed the emergence of mesothelial cells in the CRC samples, consistent with the published findings that CRC can lead to an increase in mesenchymal cells (Fig. 7b,c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Distance-to-atlas analysis distinguished cancer from normal cells, with stem cells and colonocytes showing the greatest deviation, while goblet cells remained closer to normal states (Fig. 7d,e).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Subsetting and integrating colonocytes from both normal and cancer organoids identified two distinct groups: a mixed normal–cancer cluster and a cancer-specific cluster with markedly higher atlas distances (Fig. 7f–h).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	DEG analysis revealed higher expression levels of CRC markers such as CEACAM6, SPINK1, TGFBI and RSPO3 in the cancer cell group (Fig. 7i).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Notably, recurrent R-spondin gene fusions have been described in certain patients with CRC and this event potentiates Wnt signaling and tumorigenesis.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	GO enrichment analysis highlighted immunity and cytotoxicity genes in cancer cells (Extended Data Fig. 9c).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	These analyses show the utility of distance measures to the HEOCA as a strategy to elucidate cell states that deviate healthy or otherwise normal states.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Fig. 7Comparison with the HEOCA healthy organoid cohort reveals disease-associated features.a, Overview of colorectal cancer organoid samples and their analysis through the HEOCA assessment.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	b, UMAP of adjacent normal colon and colorectal cancer samples mapped to the HEOCA colored by predicted level 2 cell type.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	c, Proportion of predicted level 2 cell type in two samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, ROC plot of cancer cell prediction using the distance to the atlas.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, Distance from adjacent normal and CRC cells to HEOCA is split by cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f, UMAP of CRC and adjacent normal colonocytes, colored by sample type (left), distance to HEOCA (middle) and predicted disease state (right).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	g, Box plot showing the distance to the atlas for the two disease-state clusters.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	h, Bar plot illustrates the distribution of CRC and adjacent normal cells in two distinct clusters of disease-state cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	i, Scatter plot showing DEGs between normal and cancer colonocytes.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	j, Overview of COPD organoid samples and their analysis through the HEOCA assessment.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	k, UMAP of normal and COPD nasopharyngeal (PO) and bronchial (BO) organoid scRNA-seq samples mapped to HEOCA, colored by predicted level 2 cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	l, Proportions of predicted level 2 cell types in normal and COPD PO and BO samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	m, ROC plot of COPD cell prediction using distance to the atlas.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	n, Distance to HEOCA for normal and COPD PO (left) and BO (right), divided by cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	o, UMAP of COPD and normal BO basal cells, colored by sample type (left), distance to HEOCA (right) and predicted disease state (bottom).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	p, Box plot presents the distance of cells to HEOCA for the two clusters of disease-state cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	q, Bar plot illustrates the distribution of normal and COPD BO basal cells in two distinct disease-state clusters.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	r, Scatter plot showing the DEGs between normal and COPD BO samples basal cell.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For plots in e, g, n and p, P values are from two-tailed Mann–Whitney U-tests.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	In the box plots in g and p, 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.	a, Overview of colorectal cancer organoid samples and their analysis through the HEOCA assessment.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	b, UMAP of adjacent normal colon and colorectal cancer samples mapped to the HEOCA colored by predicted level 2 cell type.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	c, Proportion of predicted level 2 cell type in two samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	d, ROC plot of cancer cell prediction using the distance to the atlas.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	e, Distance from adjacent normal and CRC cells to HEOCA is split by cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	f, UMAP of CRC and adjacent normal colonocytes, colored by sample type (left), distance to HEOCA (middle) and predicted disease state (right).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	g, Box plot showing the distance to the atlas for the two disease-state clusters.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	h, Bar plot illustrates the distribution of CRC and adjacent normal cells in two distinct clusters of disease-state cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	i, Scatter plot showing DEGs between normal and cancer colonocytes.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	j, Overview of COPD organoid samples and their analysis through the HEOCA assessment.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	k, UMAP of normal and COPD nasopharyngeal (PO) and bronchial (BO) organoid scRNA-seq samples mapped to HEOCA, colored by predicted level 2 cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	l, Proportions of predicted level 2 cell types in normal and COPD PO and BO samples.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	m, ROC plot of COPD cell prediction using distance to the atlas.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	n, Distance to HEOCA for normal and COPD PO (left) and BO (right), divided by cell types.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	o, UMAP of COPD and normal BO basal cells, colored by sample type (left), distance to HEOCA (right) and predicted disease state (bottom).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	p, Box plot presents the distance of cells to HEOCA for the two clusters of disease-state cells.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	q, Bar plot illustrates the distribution of normal and COPD BO basal cells in two distinct disease-state clusters.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	r, Scatter plot showing the DEGs between normal and COPD BO samples basal cell.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	For plots in e, g, n and p, P values are from two-tailed Mann–Whitney U-tests.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	In the box plots in g and p, 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.	In a second assessment, we used a publicly available dataset of two different organoid types generated from cells of patients with chronic obstructive pulmonary disease (COPD) (Fig. 7j).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	These were derived from nasopharyngeal and bronchial stem cells of these patients respectively.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Both nasopharyngeal and bronchial COPD organoids mapped to lung populations in the HEOCA, but whereas nasopharyngeal organoids resembled healthy samples, bronchial organoids exhibited an increased proportion of club cells and fewer basal cells (Fig. 7k,l).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Distance-to-atlas analysis effectively distinguished normal from COPD conditions, with the bronchial COPD organoids showing notable deviations (Fig. 7m).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	These results matched with the original publication, which showed similar differences in cell-type composition and reported differences in resistance to viral infection between the bronchial and nasopharyngeal COPD organoids.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Based on atlas similarity, we observed that the nasopharyngeal normal and COPD samples showed relatively minor differences across all cell types, whereas basal cells in the bronchial COPD samples displayed a bimodal distribution (Fig. 7n).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Distance to HEOCA states identified one basal cell population indicative of a disease state, which was further clarified in a heterogeneity analysis of basal cells from healthy and bronchial organoids (Fig. 7n–q).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	DEG analysis revealed decreased KRT5 and KRT15 expression, and high expression of genes known to be upregulated in COPD such as PSCA and BPIFB1 (Fig. 7r).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	GO enrichment analysis of the DEGs shows that disease cells have enriched expression of cilium and axoneme genes (Extended Data Fig. 9d).
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Together these data show that the HEOCA can be used to place cell states observed in organoid disease models in a larger context, which helps to better understand holistic effects on cell composition and gene expression patterns.
PMC12081310	An integrated transcriptomic cell atlas of human endoderm-derived organoids.	Finally, we provide an assessment of the viability of organoids derived from different source types (PSC, FSC, ASC) for drug target screening.

PMC12081310

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

We found that DEGs identified from comparison with the HEOCA cohort were similar to the set identified through comparison with the isogenic control (Extended Data Fig. 9a,b).

PMC12081310

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

To assess the biological relevance of the identified states, we compared transcriptomes with counterpart epithelium in an atlas of inflammatory bowel disease (IBD) patient samples.

PMC12081310

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

Interestingly, we found that the perturbation-induced DEGs were also differentially expressed between healthy individuals and patients with IBD (Fig. 6i, j).

PMC12081310

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

This finding confirms that these perturbations generate organoid cell states not prevalent in the atlas, that the integrated atlas can be used as a diverse cohort for perturbation assessment and that these perturbation states have relevance to primary counterparts.

PMC12081310

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

Fig. 6Organoid perturbation and comparison with the HEOCA extends the cell state repertoire.a, Summary of the cytokines used to treat ileum organoids for viral response and inflammation.

PMC12081310

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

The HEOCA provides a diverse cohort of cell types and states that can be used as a control for comparing perturbation conditions to reveal DEGs and under-represented cell states.

PMC12081310

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

b, UMAP of sample scRNA-seq data mapped to the HEOCA, colored by predicted level 2 cell types, from left to right: control, viral response and inflammation.

PMC12081310

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

c, Bar plot depicting the cell proportions of predicted level 2 cell types across control and cytokine treatment scRNA-seq data.

PMC12081310

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

d, UMAP of the integrated control and cytokine treatment samples, colored by sample, cell types and distance to HEOCA.

PMC12081310

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

e, Box plot comparing distance to HEOCA among control and treatment samples across different cell types.

PMC12081310

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

f, Scatter plot showing genes differentially expressed between cytokine treatment samples and the HEOCA cohorts.

PMC12081310

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

g, Dot plots displaying an example gene expression comparison of HEOCA and cytokine treatment samples across different cell types.

PMC12081310

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

h, Heatmap illustrating the DEGs GO enrichment comparison among different cytokine treatments and HEOCA cohorts.

PMC12081310

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

The P value was computed using Fisher’s exact test.

PMC12081310

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

i, Organoid perturbation expression signatures were compared for intestinal epithelial cell single-cell transcriptome data from patients with different IBDs.

PMC12081310

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

Box plots show the distribution of mean expression of genes differentially expressed between inflammatory or viral response conditions (compared with the HEOCA control cohort), and the overlap of DEGs between both conditions.

PMC12081310

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

j, Distribution of mean gene expression across IBD conditions for representative genes induced in viral response and inflammatory conditions.

PMC12081310

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

For box plots in e, i and j, P values are derived from two-tailed Mann–Whitney U-test. *

PMC12081310

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

P < 0.05, **P < 0.001, ***P < 0.001).

PMC12081310

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

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.

Inflam, infammation.

PMC12081310

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

a, Summary of the cytokines used to treat ileum organoids for viral response and inflammation.

PMC12081310

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

The HEOCA provides a diverse cohort of cell types and states that can be used as a control for comparing perturbation conditions to reveal DEGs and under-represented cell states.

PMC12081310

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

b, UMAP of sample scRNA-seq data mapped to the HEOCA, colored by predicted level 2 cell types, from left to right: control, viral response and inflammation.

PMC12081310

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

c, Bar plot depicting the cell proportions of predicted level 2 cell types across control and cytokine treatment scRNA-seq data.

PMC12081310

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

d, UMAP of the integrated control and cytokine treatment samples, colored by sample, cell types and distance to HEOCA.

PMC12081310

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

e, Box plot comparing distance to HEOCA among control and treatment samples across different cell types.

PMC12081310

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

f, Scatter plot showing genes differentially expressed between cytokine treatment samples and the HEOCA cohorts.

PMC12081310

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

g, Dot plots displaying an example gene expression comparison of HEOCA and cytokine treatment samples across different cell types.

PMC12081310

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

h, Heatmap illustrating the DEGs GO enrichment comparison among different cytokine treatments and HEOCA cohorts.

PMC12081310

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

The P value was computed using Fisher’s exact test.

PMC12081310

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

i, Organoid perturbation expression signatures were compared for intestinal epithelial cell single-cell transcriptome data from patients with different IBDs.

PMC12081310

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

Box plots show the distribution of mean expression of genes differentially expressed between inflammatory or viral response conditions (compared with the HEOCA control cohort), and the overlap of DEGs between both conditions.

PMC12081310

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

j, Distribution of mean gene expression across IBD conditions for representative genes induced in viral response and inflammatory conditions.

PMC12081310

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

For box plots in e, i and j, P values are derived from two-tailed Mann–Whitney U-test. *

PMC12081310

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

P < 0.05, **P < 0.001, ***P < 0.001).

PMC12081310

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

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.

Inflam, infammation.

PMC12081310

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

We next assessed the utility of the integrated atlas to understand organoid models of disease.

PMC12081310

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

Through comparison with the HEOCA we assess cell proportion, identify disease-associated states and perform differential expression analysis against the atlas data (Fig. 5a).

PMC12081310

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

We first explored colorectal cancer (CRC) using a dataset composed of CRC organoids from a patient resection and normal organoids from adjacent healthy tissue (Fig. 7a).

PMC12081310

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

HEOCA mapping analysis showed that CRC samples exhibited a lower percentage of mature colonocytes, and a higher proportion of stem cells (Fig. 7b,c).

PMC12081310

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

Interestingly, we also observed the emergence of mesothelial cells in the CRC samples, consistent with the published findings that CRC can lead to an increase in mesenchymal cells (Fig. 7b,c).

PMC12081310

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

Distance-to-atlas analysis distinguished cancer from normal cells, with stem cells and colonocytes showing the greatest deviation, while goblet cells remained closer to normal states (Fig. 7d,e).

PMC12081310

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

Subsetting and integrating colonocytes from both normal and cancer organoids identified two distinct groups: a mixed normal–cancer cluster and a cancer-specific cluster with markedly higher atlas distances (Fig. 7f–h).

PMC12081310

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

DEG analysis revealed higher expression levels of CRC markers such as CEACAM6, SPINK1, TGFBI and RSPO3 in the cancer cell group (Fig. 7i).

PMC12081310

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

Notably, recurrent R-spondin gene fusions have been described in certain patients with CRC and this event potentiates Wnt signaling and tumorigenesis.

PMC12081310

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

GO enrichment analysis highlighted immunity and cytotoxicity genes in cancer cells (Extended Data Fig. 9c).

PMC12081310

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

These analyses show the utility of distance measures to the HEOCA as a strategy to elucidate cell states that deviate healthy or otherwise normal states.

PMC12081310

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

Fig. 7Comparison with the HEOCA healthy organoid cohort reveals disease-associated features.a, Overview of colorectal cancer organoid samples and their analysis through the HEOCA assessment.

PMC12081310

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

b, UMAP of adjacent normal colon and colorectal cancer samples mapped to the HEOCA colored by predicted level 2 cell type.

PMC12081310

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

c, Proportion of predicted level 2 cell type in two samples.

PMC12081310

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

d, ROC plot of cancer cell prediction using the distance to the atlas.

PMC12081310

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

e, Distance from adjacent normal and CRC cells to HEOCA is split by cell types.

PMC12081310

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

f, UMAP of CRC and adjacent normal colonocytes, colored by sample type (left), distance to HEOCA (middle) and predicted disease state (right).

PMC12081310

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

g, Box plot showing the distance to the atlas for the two disease-state clusters.

PMC12081310

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

h, Bar plot illustrates the distribution of CRC and adjacent normal cells in two distinct clusters of disease-state cells.

PMC12081310

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

i, Scatter plot showing DEGs between normal and cancer colonocytes.

PMC12081310

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

j, Overview of COPD organoid samples and their analysis through the HEOCA assessment.

PMC12081310

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

k, UMAP of normal and COPD nasopharyngeal (PO) and bronchial (BO) organoid scRNA-seq samples mapped to HEOCA, colored by predicted level 2 cell types.

PMC12081310

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

l, Proportions of predicted level 2 cell types in normal and COPD PO and BO samples.

PMC12081310

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

m, ROC plot of COPD cell prediction using distance to the atlas.

PMC12081310

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

n, Distance to HEOCA for normal and COPD PO (left) and BO (right), divided by cell types.

PMC12081310

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

o, UMAP of COPD and normal BO basal cells, colored by sample type (left), distance to HEOCA (right) and predicted disease state (bottom).

PMC12081310

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

p, Box plot presents the distance of cells to HEOCA for the two clusters of disease-state cells.

PMC12081310

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

q, Bar plot illustrates the distribution of normal and COPD BO basal cells in two distinct disease-state clusters.

PMC12081310

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

r, Scatter plot showing the DEGs between normal and COPD BO samples basal cell.

PMC12081310

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

For plots in e, g, n and p, P values are from two-tailed Mann–Whitney U-tests.

PMC12081310

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

In the box plots in g and p, 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.

a, Overview of colorectal cancer organoid samples and their analysis through the HEOCA assessment.

PMC12081310

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

b, UMAP of adjacent normal colon and colorectal cancer samples mapped to the HEOCA colored by predicted level 2 cell type.

PMC12081310

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

c, Proportion of predicted level 2 cell type in two samples.

PMC12081310

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

d, ROC plot of cancer cell prediction using the distance to the atlas.

PMC12081310

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

e, Distance from adjacent normal and CRC cells to HEOCA is split by cell types.

PMC12081310

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

f, UMAP of CRC and adjacent normal colonocytes, colored by sample type (left), distance to HEOCA (middle) and predicted disease state (right).

PMC12081310

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

g, Box plot showing the distance to the atlas for the two disease-state clusters.

PMC12081310

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

h, Bar plot illustrates the distribution of CRC and adjacent normal cells in two distinct clusters of disease-state cells.

PMC12081310

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

i, Scatter plot showing DEGs between normal and cancer colonocytes.

PMC12081310

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

j, Overview of COPD organoid samples and their analysis through the HEOCA assessment.

PMC12081310

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

k, UMAP of normal and COPD nasopharyngeal (PO) and bronchial (BO) organoid scRNA-seq samples mapped to HEOCA, colored by predicted level 2 cell types.

PMC12081310

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

l, Proportions of predicted level 2 cell types in normal and COPD PO and BO samples.

PMC12081310

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

m, ROC plot of COPD cell prediction using distance to the atlas.

PMC12081310

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

n, Distance to HEOCA for normal and COPD PO (left) and BO (right), divided by cell types.

PMC12081310

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

o, UMAP of COPD and normal BO basal cells, colored by sample type (left), distance to HEOCA (right) and predicted disease state (bottom).

PMC12081310

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

p, Box plot presents the distance of cells to HEOCA for the two clusters of disease-state cells.

PMC12081310

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

q, Bar plot illustrates the distribution of normal and COPD BO basal cells in two distinct disease-state clusters.

PMC12081310

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

r, Scatter plot showing the DEGs between normal and COPD BO samples basal cell.

PMC12081310

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

For plots in e, g, n and p, P values are from two-tailed Mann–Whitney U-tests.

PMC12081310

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

In the box plots in g and p, 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.

In a second assessment, we used a publicly available dataset of two different organoid types generated from cells of patients with chronic obstructive pulmonary disease (COPD) (Fig. 7j).

PMC12081310

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

These were derived from nasopharyngeal and bronchial stem cells of these patients respectively.

PMC12081310

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

Both nasopharyngeal and bronchial COPD organoids mapped to lung populations in the HEOCA, but whereas nasopharyngeal organoids resembled healthy samples, bronchial organoids exhibited an increased proportion of club cells and fewer basal cells (Fig. 7k,l).

PMC12081310

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

Distance-to-atlas analysis effectively distinguished normal from COPD conditions, with the bronchial COPD organoids showing notable deviations (Fig. 7m).

PMC12081310

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

These results matched with the original publication, which showed similar differences in cell-type composition and reported differences in resistance to viral infection between the bronchial and nasopharyngeal COPD organoids.

PMC12081310

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

Based on atlas similarity, we observed that the nasopharyngeal normal and COPD samples showed relatively minor differences across all cell types, whereas basal cells in the bronchial COPD samples displayed a bimodal distribution (Fig. 7n).

PMC12081310

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

Distance to HEOCA states identified one basal cell population indicative of a disease state, which was further clarified in a heterogeneity analysis of basal cells from healthy and bronchial organoids (Fig. 7n–q).

PMC12081310

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

DEG analysis revealed decreased KRT5 and KRT15 expression, and high expression of genes known to be upregulated in COPD such as PSCA and BPIFB1 (Fig. 7r).

PMC12081310

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

GO enrichment analysis of the DEGs shows that disease cells have enriched expression of cilium and axoneme genes (Extended Data Fig. 9d).

PMC12081310

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

Together these data show that the HEOCA can be used to place cell states observed in organoid disease models in a larger context, which helps to better understand holistic effects on cell composition and gene expression patterns.

PMC12081310

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

Finally, we provide an assessment of the viability of organoids derived from different source types (PSC, FSC, ASC) for drug target screening.