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SS18 regulates pluripotent-somatic transition through phase separation.

Junqi Kuang1,2,3, Ziwei Zhai1,2,3, Pengli Li1,2,3

  • 1CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

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|July 3, 2021
PubMed
Summary
This summary is machine-generated.

SS18 regulates the critical pluripotent to somatic transition (PST) in mammalian development by forming nuclear condensates. This process involves liquid-liquid phase separation mediated by SS18

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Area of Science:

  • Developmental Biology
  • Cellular Biology
  • Molecular Biology

Background:

  • The transition from pluripotent to somatic cell states is fundamental to mammalian development but poorly understood.
  • Identifying key regulators of this developmental switch is crucial for understanding cellular differentiation.

Purpose of the Study:

  • To identify novel regulators of the pluripotent to somatic transition (PST).
  • To elucidate the molecular mechanisms by which SS18 controls PST.

Main Methods:

  • CRISPR-based whole-genome screens were employed to identify PST regulators.
  • Mutagenesis studies were performed to investigate the function of SS18 domains.
  • Biochemical assays were used to analyze protein interactions and complex assembly.

Main Results:

  • SS18 was identified as a critical regulator of PST.
  • SS18 forms nuclear condensates via a tyrosine-rich intrinsically disordered region (IDR).
  • The N-terminal region of SS18 interacts with the Brg/Brahma-associated factor (BAF) complex, mediating BAF assembly through phase separation.

Conclusions:

  • SS18 plays a pivotal role at the pluripotent-somatic interface.
  • SS18 utilizes a unique tyrosine-based liquid-liquid phase separation mechanism to regulate PST.
  • The findings provide new insights into the molecular control of cell fate decisions during development.