Pluripotency-independent induction of human trophoblast stem cells from fibroblasts.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 06 2023
08 06 2023
Historique:
received:
03
11
2021
accepted:
30
05
2023
medline:
12
6
2023
pubmed:
9
6
2023
entrez:
8
6
2023
Statut:
epublish
Résumé
Human trophoblast stem cells (hTSCs) can be derived from embryonic stem cells (hESCs) or be induced from somatic cells by OCT4, SOX2, KLF4 and MYC (OSKM). Here we explore whether the hTSC state can be induced independently of pluripotency, and what are the mechanisms underlying its acquisition. We identify GATA3, OCT4, KLF4 and MYC (GOKM) as a combination of factors that can generate functional hiTSCs from fibroblasts. Transcriptomic analysis of stable GOKM- and OSKM-hiTSCs reveals 94 hTSC-specific genes that are aberrant specifically in OSKM-derived hiTSCs. Through time-course-RNA-seq analysis, H3K4me2 deposition and chromatin accessibility, we demonstrate that GOKM exert greater chromatin opening activity than OSKM. While GOKM primarily target hTSC-specific loci, OSKM mainly induce the hTSC state via targeting hESC and hTSC shared loci. Finally, we show that GOKM efficiently generate hiTSCs from fibroblasts that harbor knockout for pluripotency genes, further emphasizing that pluripotency is dispensable for hTSC state acquisition.
Identifiants
pubmed: 37291192
doi: 10.1038/s41467-023-39104-1
pii: 10.1038/s41467-023-39104-1
pmc: PMC10250329
doi:
Substances chimiques
Chromatin
0
Octamer Transcription Factor-3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3359Subventions
Organisme : Howard Hughes Medical Institute
ID : 55008727
Pays : United States
Informations de copyright
© 2023. The Author(s).
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