Low complexity domains, condensates, and stem cell pluripotency

doi:10.4252/wjsc.v13.i5.416

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May 26, 2021 (publication date) through Feb 26, 2026

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World Journal of Stem Cells

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1948-0210

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World J Stem Cells. May 26, 2021; 13(5): 416-438
Published online May 26, 2021. doi: 10.4252/wjsc.v13.i5.416

Low complexity domains, condensates, and stem cell pluripotency

Munender Vodnala, Eun-Bee Choi, Yick W Fong

Munender Vodnala, Eun-Bee Choi, Yick W Fong, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States

Yick W Fong, Harvard Stem Cell Institute, Cambridge, MA 02138, United States

Author contributions: Fong YW, Vodnala M and Choi EB wrote and edited the manuscript; Vodnala M made the figures and table; all authors have read and approved the final manuscript.

Supported by National Institute of Health, No. R01HL125527.

Conflict-of-interest statement: The authors declare no conflict of interests for this article.

Corresponding author: Yick W Fong, PhD, Assistant Professor, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States. yfong@bwh.harvard.edu

Received: March 10, 2021
Peer-review started: March 10, 2021
First decision: April 19, 2021
Revised: April 20, 2021
Accepted: April 28, 2021
Article in press: April 28, 2021
Published online: May 26, 2021
Processing time: 76 Days and 13.9 Hours

Abstract

Biological reactions require self-assembly of factors in the complex cellular milieu. Recent evidence indicates that intrinsically disordered, low-complexity sequence domains (LCDs) found in regulatory factors mediate diverse cellular processes from gene expression to DNA repair to signal transduction, by enriching specific biomolecules in membraneless compartments or hubs that may undergo liquid-liquid phase separation (LLPS). In this review, we discuss how embryonic stem cells take advantage of LCD-driven interactions to promote cell-specific transcription, DNA damage response, and DNA repair. We propose that LCD-mediated interactions play key roles in stem cell maintenance and safeguarding genome integrity.

Keywords: Liquid-liquid phase separation; Embryonic stem cell; Pluripotency; Low complexity domain; Transcription; DNA damage response

Core Tip: This review article discusses recent findings regarding the role of low-complexity domain proteins and phase separation in regulating key cellular processes in embryonic stem cells, including transcriptional activation and repression, cellular signaling integration, DNA damage response, and DNA repair.