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Low complexity domains, condensates, and stem cell pluripotency.

Munender Vodnala1, Eun-Bee Choi1, Yick W Fong1

  • 1Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.

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|June 17, 2021
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Summary

Embryonic stem cells utilize intrinsically disordered, low-complexity sequence domains (LCDs) to form cellular compartments. These LCD-driven interactions are crucial for maintaining stem cell function and protecting their genome.

Keywords:
DNA damage responseEmbryonic stem cellLiquid-liquid phase separationLow complexity domainPluripotencyTranscription

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Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Biological reactions rely on the self-assembly of factors within the cellular environment.
  • Intrinsically disordered, low-complexity sequence domains (LCDs) in regulatory factors are increasingly recognized for their role in diverse cellular processes.
  • These domains facilitate the formation of membraneless compartments or hubs through mechanisms like liquid-liquid phase separation (LLPS), enriching specific biomolecules.

Purpose of the Study:

  • To review the role of intrinsically disordered, low-complexity sequence domains (LCDs) in embryonic stem cell biology.
  • To explore how LCD-driven interactions promote cell-specific transcription, DNA damage response, and DNA repair in embryonic stem cells.
  • To propose the significance of LCD-mediated interactions in stem cell maintenance and genome integrity.

Main Methods:

  • This is a review article, synthesizing existing evidence.
  • The review focuses on the functional implications of LCDs in embryonic stem cells.
  • Literature search and analysis of studies investigating LCDs, LLPS, and stem cell biology.

Main Results:

  • LCDs enable the formation of dynamic, membraneless compartments within cells.
  • Embryonic stem cells leverage LCD-driven interactions for specialized transcription and robust DNA repair mechanisms.
  • These interactions are vital for maintaining the unique properties and genomic stability of stem cells.

Conclusions:

  • LCD-mediated interactions are fundamental to the specialized functions of embryonic stem cells.
  • These interactions play a critical role in stem cell maintenance and the safeguarding of genome integrity.
  • Understanding LCDs offers insights into stem cell biology and potential therapeutic strategies.