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Ori, C. ; Ansari, M. ; Angelidis, I. ; Olmer, R.* ; Martin, U.* ; Theis, F.J. ; Schiller, H. B. ; Drukker, M.

Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors.

iScience 26:108205 (2023)
Verlagsversion DOI PMC
Creative Commons Lizenzvertrag
In this study, we interrogate molecular mechanisms underlying the specification of lung progenitors from human pluripotent stem cells (hPSCs). We employ single-cell RNA-sequencing with high temporal precision, alongside an optimized differentiation protocol, to elucidate the transcriptional hierarchy of lung specification to chart the associated single-cell trajectories. Our findings indicate that Sonic hedgehog, TGF-β, and Notch activation are essential within an ISL1/NKX2-1 trajectory, leading to the emergence of lung progenitors during the foregut endoderm phase. Additionally, the induction of HHEX delineates an alternate trajectory at the early definitive endoderm stage, preceding the lung pathway and giving rise to a significant hepatoblast population. Intriguingly, neither KDR+ nor mesendoderm progenitors manifest as intermediate stages in the lung and hepatic lineage development. Our multistep model offers insights into lung organogenesis and provides a foundation for in-depth study of early human lung development and modeling using hPSCs.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cell Biology ; Developmental Biology ; Molecular Biology; Efficient Derivation; Sonic Hedgehog; Homeobox Gene; In-vitro; Liver; Differentiation; Endoderm; Foxa2; Catenin; Pathway
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Zeitschrift iScience
Quellenangaben Band: 26, Heft: 11, Seiten: , Artikelnummer: 108205 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
Lung Health and Immunity (LHI)
Institute of Computational Biology (ICB)
Förderungen German Center for Lung Research (DZL)
Helmholtz Association