ID proteins promote the survival and primed-to-naive transition of human embryonic stem cells through TCF3-mediated transcription.
Authors
Jiang, Haibin
Du, Mingxia
Li, Yaning
Zhou, Tengfei
Lei, Jia
Liang, Hongqing
Zhong, Zhen
Al-Lamki, Rafia S
Jiang, Ming
Publication Date
2022-06-15Journal Title
Cell Death Dis
ISSN
2041-4889
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
6
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Jiang, H., Du, M., Li, Y., Zhou, T., Lei, J., Liang, H., Zhong, Z., et al. (2022). ID proteins promote the survival and primed-to-naive transition of human embryonic stem cells through TCF3-mediated transcription.. Cell Death Dis, 13 (6) https://doi.org/10.1038/s41419-022-04958-8
Description
Funder: National Key Research and Development Program of China Stem Cell and Translational Research, 2016YFA0102300
Funder: Zhejiang University Education Foundation Global Partnership Fund(188170+194452115/011)
Abstract
Inhibition of DNA binding proteins 1 and 3 (ID1 and ID3) are important downstream targets of BMP signalling that are necessary for embryonic development. However, their specific roles in regulating the pluripotency of human embryonic stem cells (hESCs) remain unclear. Here, we examined the roles of ID1 and ID3 in primed and naive-like hESCs and showed that ID1 and ID3 knockout lines (IDs KO) exhibited decreased survival in both primed and naive-like state. IDs KO lines in the primed state also tended to undergo pluripotent dissolution and ectodermal differentiation. IDs KO impeded the primed-to-naive transition (PNT) of hESCs, and overexpression of ID1 in primed hESCs promoted PNT. Furthermore, single-cell RNA sequencing demonstrated that ID1 and ID3 regulated the survival and pluripotency of hESCs through the AKT signalling pathway. Finally, we showed that TCF3 mediated transcriptional inhibition of MCL1 promotes AKT phosphorylation, which was confirmed by TCF3 knockdown in KO lines. Our study suggests that IDs/TCF3 acts through AKT signalling to promote survival and maintain pluripotency of both primed and naive-like hESCs.
Keywords
Article, /631/80/86/2364, /631/532/2117, /38, /38/39, /82, /82/80, /96, /96/100, article
Identifiers
s41419-022-04958-8, 4958
External DOI: https://doi.org/10.1038/s41419-022-04958-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338122
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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