Cargando…
Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors
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 hierarch...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663741/ https://www.ncbi.nlm.nih.gov/pubmed/38026193 http://dx.doi.org/10.1016/j.isci.2023.108205 |
_version_ | 1785138465495580672 |
---|---|
author | Ori, Chaido Ansari, Meshal Angelidis, Ilias Olmer, Ruth Martin, Ulrich Theis, Fabian J. Schiller, Herbert B. Drukker, Micha |
author_facet | Ori, Chaido Ansari, Meshal Angelidis, Ilias Olmer, Ruth Martin, Ulrich Theis, Fabian J. Schiller, Herbert B. Drukker, Micha |
author_sort | Ori, Chaido |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10663741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-106637412023-10-14 Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors Ori, Chaido Ansari, Meshal Angelidis, Ilias Olmer, Ruth Martin, Ulrich Theis, Fabian J. Schiller, Herbert B. Drukker, Micha iScience Article 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. Elsevier 2023-10-14 /pmc/articles/PMC10663741/ /pubmed/38026193 http://dx.doi.org/10.1016/j.isci.2023.108205 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ori, Chaido Ansari, Meshal Angelidis, Ilias Olmer, Ruth Martin, Ulrich Theis, Fabian J. Schiller, Herbert B. Drukker, Micha Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors |
title | Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors |
title_full | Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors |
title_fullStr | Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors |
title_full_unstemmed | Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors |
title_short | Human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors |
title_sort | human pluripotent stem cell fate trajectories toward lung and hepatocyte progenitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663741/ https://www.ncbi.nlm.nih.gov/pubmed/38026193 http://dx.doi.org/10.1016/j.isci.2023.108205 |
work_keys_str_mv | AT orichaido humanpluripotentstemcellfatetrajectoriestowardlungandhepatocyteprogenitors AT ansarimeshal humanpluripotentstemcellfatetrajectoriestowardlungandhepatocyteprogenitors AT angelidisilias humanpluripotentstemcellfatetrajectoriestowardlungandhepatocyteprogenitors AT olmerruth humanpluripotentstemcellfatetrajectoriestowardlungandhepatocyteprogenitors AT martinulrich humanpluripotentstemcellfatetrajectoriestowardlungandhepatocyteprogenitors AT theisfabianj humanpluripotentstemcellfatetrajectoriestowardlungandhepatocyteprogenitors AT schillerherbertb humanpluripotentstemcellfatetrajectoriestowardlungandhepatocyteprogenitors AT drukkermicha humanpluripotentstemcellfatetrajectoriestowardlungandhepatocyteprogenitors |