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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)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Cell Biology ; Developmental Biology ; Molecular Biology; Efficient Derivation; Sonic Hedgehog; Homeobox Gene; In-vitro; Liver; Differentiation; Endoderm; Foxa2; Catenin; Pathway
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Journal iScience
Quellenangaben Volume: 26, Issue: 11, Pages: , Article Number: 108205 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status Peer reviewed
Institute(s) 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
Research field(s) Stem Cell and Neuroscience
Lung Research
Enabling and Novel Technologies
PSP Element(s) G-500893-001
G-501800-810
G-503800-001
Grants 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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