An integrated transcriptomic cell atlas of human endoderm-derived organoids

Human pluripotent stem cells and tissue-resident fetal and adult stem cells can generate epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology. Here, we integrate single-cell transcriptomes from 218 samples covering organoids and other models of diverse endoderm-derived tissues to establish an initial version of a human endoderm-derived organoid cell atlas (HEOCA). The integration includes nearly one million cells across diverse conditions, data sources and protocols. We compare cell types and states between organoid models, and harmonize cell annotations through mapping to primary tissue counterparts. Focusing on the intestine and lung, we provide examples of mapping data from new protocols, and show how the atlas can be used as a diverse cohort to assess perturbations and disease models. The HEOCA makes diverse datasets centrally available, and will be valuable to assess fidelity, characterize perturbed and diseased states, and streamline protocol development. Ileal organoids derived from human tissue samples were subjected to either control conditions or different growth factors (TNFα + RANKL for increased microfold cells or IL-4 + IL-13 for increased tuft cells), viral response cytokines (IFNα + IFNγ and IFNβ) and inflammatory agents (TNFα + IL-6 + IL-17A + IFNγ + IL-18 + OSM + SCF). scRNAseq experiments were performed to study the differentiation and cellular profile under these different conditions. *************************************************************** Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access. ***************************************************************