Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors.
iScience
; 26(11): 108205, 2023 Nov 17.
Article
en En
| MEDLINE
| ID: mdl-38026193
ABSTRACT
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-ß, 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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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
IScience
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania