Leveraging interacting signaling pathways to robustly improve the quality and yield of human pluripotent stem cell-derived hepatoblasts and hepatocytes.
differentiation
disease modeling
drug discovery
hepatoblasts
hepatocyte-like cells
human
induced pluripotent stem cells
liver development
liver organoids
pluripotent stem cells
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
08 03 2022
08 03 2022
Historique:
received:
10
08
2020
revised:
04
01
2022
accepted:
05
01
2022
pubmed:
6
2
2022
medline:
3
5
2022
entrez:
5
2
2022
Statut:
ppublish
Résumé
Pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs) have shown great potential as an alternative to primary human hepatocytes (PHHs) for in vitro modeling. Several differentiation protocols have been described to direct PSCs toward the hepatic fate. Here, by leveraging recent knowledge of the signaling pathways involved in liver development, we describe a robust, scalable protocol that allowed us to consistently generate high-quality bipotent human hepatoblasts and HLCs from both embryonic stem cells and induced PSC (iPSCs). Although not yet fully mature, such HLCs were more similar to adult PHHs than were cells obtained with previously described protocols, showing good potential as a physiologically representative alternative to PHHs for in vitro modeling. PSC-derived hepatoblasts effectively generated with this protocol could differentiate into mature hepatocytes and cholangiocytes within syngeneic liver organoids, thus opening the way for representative human 3D in vitro modeling of liver development and pathophysiology.
Identifiants
pubmed: 35120625
pii: S2213-6711(22)00047-9
doi: 10.1016/j.stemcr.2022.01.003
pmc: PMC9039749
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
584-598Subventions
Organisme : CIHR
ID : MY6-155373
Pays : Canada
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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