TY - RPRT
AU - Quan Xu
AU - Lennard Halle
AU - Soroor Hediyeh-zadeh
AU - Merel Kuijs
AU - Umut Kilik
AU - Qianhui Yu
AU - Tristan Frum
AU - Lukas Adam
AU - Shrey Parikh
AU - Manuel Gander
AU - Raphael Kfuri-Rubens
AU - Dominik Klein
AU - Zhisong He
AU - Jonas Simon Fleck
AU - Koen Oost
AU - Maurice Kahnwald
AU - Silvia Barbiero
AU - Olga Mitrofanova
AU - Grzegorz Maciag
AU - Kim B. Jensen
AU - Matthias Lutolf
AU - Prisca Liberali
AU - Joep Beumer
AU - Jason R. Spence
AU - Barbara Treutlein
AU - Fabian J. Theis
AU - J. Gray Camp
AB - Human stem cells can generate complex, multicellular epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology. These tissues, also called organoids, can be derived from pluripotent stem cells or tissue-resident fetal and adult stem cells. However, it has remained difficult to understand the precision and accuracy of organoid cell states through comparison with primary counterparts, and to comprehensively assess the similarity and differences between organoid protocols. Advances in computational single-cell biology now allow the integration of datasets with high technical variability. Here, we integrate single-cell transcriptomes from 218 samples covering organoids of diverse endoderm-derived tissues including lung, pancreas, intestine, liver, biliary system, stomach, and prostate to establish an initial version of a human endoderm organoid cell atlas (HEOCA). The integration includes nearly one million cells across diverse conditions, data sources and protocols. We align and compare cell types and states between organoid models, and harmonize cell type annotations by mapping the atlas to primary tissue counterparts. To demonstrate utility of the atlas, we focus on intestine and lung, and clarify ontogenic cell states that can be modeled in vitro. We further provide examples of mapping novel data from new organoid protocols to expand the atlas, and showcase how integrating organoid models of disease into the HEOCA identifies altered cell proportions and states between healthy and disease conditions. The atlas makes diverse datasets centrally available, and will be valuable to assess organoid fidelity, characterize perturbed and diseased states, and streamline protocol development.
DA - 2023-12-04
DO - 10.1101/2023.11.20.567825
LA - en
N2 - Human stem cells can generate complex, multicellular epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology. These tissues, also called organoids, can be derived from pluripotent stem cells or tissue-resident fetal and adult stem cells. However, it has remained difficult to understand the precision and accuracy of organoid cell states through comparison with primary counterparts, and to comprehensively assess the similarity and differences between organoid protocols. Advances in computational single-cell biology now allow the integration of datasets with high technical variability. Here, we integrate single-cell transcriptomes from 218 samples covering organoids of diverse endoderm-derived tissues including lung, pancreas, intestine, liver, biliary system, stomach, and prostate to establish an initial version of a human endoderm organoid cell atlas (HEOCA). The integration includes nearly one million cells across diverse conditions, data sources and protocols. We align and compare cell types and states between organoid models, and harmonize cell type annotations by mapping the atlas to primary tissue counterparts. To demonstrate utility of the atlas, we focus on intestine and lung, and clarify ontogenic cell states that can be modeled in vitro. We further provide examples of mapping novel data from new organoid protocols to expand the atlas, and showcase how integrating organoid models of disease into the HEOCA identifies altered cell proportions and states between healthy and disease conditions. The atlas makes diverse datasets centrally available, and will be valuable to assess organoid fidelity, characterize perturbed and diseased states, and streamline protocol development.
PY - 2023
TI - An integrated transcriptomic cell atlas of human endoderm-derived organoids
UR - https://www.biorxiv.org/content/10.1101/2023.11.20.567825v2
Y2 - 2024-08-13
ER -