Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 586, Issue -, Pages 163-170Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.11.060
Keywords
SOX2; DNA repair protein; PARP1; Pluripotent stem cell; Neural progenitor cell; Embryonic stem cell; Transcriptional regulation
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Funding
- National Key Research and Development Program of China [2016YFA0100303, 2016YFA0101201]
- Independent Task of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases
- First Affiliated Hospital, School of Medicine, Zhejiang University [b2019, b3444]
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The study revealed the crucial role of SOX2 interaction with DNA repair proteins in regulating neural progenitor cells, and significant up-regulation of biomarkers transcriptionally suppressed by the SOX2/DNA repair protein complexes can be achieved by down-regulating two DNA repair proteins.
SOX2, a well-established pluripotency factor supporting the self-renewal of pluripotent stem cells (PSCs), is also a crucial factor for maintaining the properties and functionalities of neural progenitor cells (NPCs). It regulates the transcription of target genes by forming complexes with its partner factors, but systematic comparison of SOX2 binding partners in human PSCs versus NPCs is lacking. Here, by deciphering and comparing the SOX2-protein interactomes in human embryonic stem cells (hESCs) versus the NPCs derived from them, we identified 23 proteins with high reproducibility that are most differentially associated with SOX2, of which 9 are DNA repair proteins (PARP1, PARP2, PRKDC, XRCC1, XRCC5, XRCC6, RPA1, LIG3, DDB1). Genetic knocking-down or pharmacological inhibiting two of the DNA repair proteins (PARP1 and PRKDC) significantly up-regulated certain NPC or ectodermal biomarkers that are transcriptionally-suppressed by the SOX2/DNA repair protein complexes. These findings point to a crucial role of DNA repair proteins in pluripotent state transition and neural induction. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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