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Autophagy modulates cell fate decisions during lineage commitment.

Kulbhushan Sharma1,2,3, Nagham T Asp1,2, Sean Harrison4

  • 1Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Autophagy
|December 20, 2021
PubMed
Summary

Autophagy

Keywords:
AutophagosomeSOX2differentiationectodermendodermmesodermpluripotent stem cells

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Cellular processes

Background:

  • Pluripotency exit and germ layer commitment are critical developmental events.
  • Autophagy plays a known role in development and differentiation.

Purpose of the Study:

  • To investigate the role of autophagy in early lineage commitment.
  • To understand how autophagy influences pluripotency exit and germ layer specification.

Main Methods:

  • Utilized human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs).
  • Manipulated autophagy levels using chemical inhibitors and genetic approaches.
  • Assessed SOX2 protein levels and lineage markers.

Main Results:

  • A decrease in autophagy facilitates exit from pluripotency.
  • Modulating autophagy impacts SOX2 levels and lineage commitment.
  • Autophagy induction promotes SOX2 degradation and mesendoderm formation.
  • Autophagy inhibition leads to SOX2 accumulation and neuroectoderm formation.

Conclusions:

  • Autophagy-mediated SOX2 turnover is a key determinant of lineage commitment.
  • Understanding this mechanism can improve derivation of specific cell types.
  • This study provides insights into early developmental pathways.