Genomic Integrity Safeguards Self-Renewal in Embryonic Stem Cells | Zendy

Jie Su | Zendy; Dandan Zhu | Zendy; Zijun Huo | Zendy; Julian A. Gingold | Zendy; Yen-Sin Ang | Zendy; Jian Tu | Zendy; Ruoji Zhou | Zendy; Yu Lin | Zendy; Haidan Luo | Zendy; Huiling Yang | Zendy; Ruiying Zhao | Zendy; Christoph Schaniel | Zendy; Kateri Moore | Zendy; Ihor R. Lemischka | Zendy; DungFang Lee | Zendy

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Genomic Integrity Safeguards Self-Renewal in Embryonic Stem Cells

Author(s) -

Jie Su,

Dandan Zhu,

Zijun Huo,

Julian A. Gingold,

Yen-Sin Ang,

Jian Tu,

Ruoji Zhou,

Yu Lin,

Haidan Luo,

Huiling Yang,

Ruiying Zhao,

Christoph Schaniel,

Kateri Moore,

Ihor R. Lemischka,

DungFang Lee

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.07.011

Subject(s) - embryonic stem cell , biology , genome instability , gene knockdown , stem cell , microbiology and biotechnology , small hairpin rna , dna damage , cellular differentiation , gene expression profiling , cell fate determination , genetics , gene , computational biology , gene expression , dna , transcription factor

A multitude of signals are coordinated to maintain self-renewal in embryonic stem cells (ESCs). To unravel the essential internal and external signals required for sustaining the ESC state, we expand upon a set of ESC pluripotency-associated phosphoregulators (PRs) identified previously by short hairpin RNA (shRNA) screening. In addition to the previously described Aurka, we identify 4 additional PRs (Bub1b, Chek1, Ppm1g, and Ppp2r1b) whose depletion compromises self-renewal and leads to consequent differentiation. Global gene expression profiling and computational analyses reveal that knockdown of the 5 PRs leads to DNA damage/genome instability, activating p53 and culminating in ESC differentiation. Similarly, depletion of genome integrity-associated genes involved in DNA replication and checkpoint, mRNA processing, and Charcot-Marie-Tooth disease lead to compromise of ESC self-renewal via an increase in p53 activity. Our studies demonstrate an essential link between genomic integrity and developmental cell fate regulation in ESCs.

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