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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
Schlagwörter Cell Biology ; Developmental Biology ; Molecular Biology; Efficient Derivation; Sonic Hedgehog; Homeobox Gene; In-vitro; Liver; Differentiation; Endoderm; Foxa2; Catenin; Pathway
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
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
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
German Center for Lung Research (DZL)
Institute of Computational Biology (ICB)
POF Topic(s) 30204 - Cell Programming and Repair
80000 - German Center for Lung Research
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Stem Cell and Neuroscience
Lung Research
Enabling and Novel Technologies
PSP-Element(e) G-500893-001
G-501800-810
G-503800-001
Förderungen German Center for Lung Research (DZL)
Helmholtz Association
DOI 10.1016/j.isci.2023.108205
WOS ID 001110938800001
Scopus ID 85176601573
PubMed ID 38026193
Erfassungsdatum 2023-11-28
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