Tuning FOXD3 expression dose-dependently balances human embryonic stem cells between pluripotency and meso-endoderm fates.
Dose-dependent
FOXD3
Human embryonic stem cells
Meso-endoderm
Pluripotency
Journal
Biochimica et biophysica acta. Molecular cell research
ISSN: 1879-2596
Titre abrégé: Biochim Biophys Acta Mol Cell Res
Pays: Netherlands
ID NLM: 101731731
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
29
01
2019
revised:
31
07
2019
accepted:
05
08
2019
pubmed:
16
8
2019
medline:
17
3
2020
entrez:
16
8
2019
Statut:
ppublish
Résumé
Forkhead box D3 (FOXD3) is a key transcription factor maintaining pluripotency in mouse embryonic stem cells (ESCs). Yet to date studies on its role in human ESCs are quite limited. In this study, we report that deletion of FOXD3 in human ESCs results in loss of pluripotency and spontaneous differentiation toward meso-endoderm. Ectopic overexpression of FOXD3 in hESCs leads to two different phenotypes: Human ESCs expressing high levels of FOXD3 undergo spontaneous meso-endoderm differentiation, whereas those with lower levels of FOXD3 maintain pluripotency. Next we deleted endogenous FOXD3 in the low ectopic expression model and find that addition of exogenous FOXD3 at a low level could rescue FOXD3-deficiency phenotype in hESCs. In summary, our findings suggest that FOXD3 dose-dependently regulates the balance of human ESCs between pluripotency and meso-endoderm fates, which adds to our understanding of the role of FOXD3 in humans.
Identifiants
pubmed: 31415841
pii: S0167-4889(19)30145-4
doi: 10.1016/j.bbamcr.2019.118531
pii:
doi:
Substances chimiques
FOXD3 protein, human
0
Forkhead Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
118531Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.