2. Academic Validation
  3. Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells

Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells

  • Science. 2020 Jul 24;369(6502):397-403. doi: 10.1126/science.abb4467.
Yi Xu 1,  Yang Zhang 1,  Juan C García-Cañaveras 2,  Lili Guo 3,  Mengyuan Kan 4,  Sixiang Yu 1,  Ian A Blair 3,  Joshua D Rabinowitz 2,  Xiaolu Yang 5
Affiliations

Affiliations

  • 1 Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 2 Lewis-Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Princeton, NJ 08540, USA.
  • 3 Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 4 Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 5 Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. xyang@pennmedicine.upenn.edu.
PMID: 32703873 DOI: 10.1126/science.abb4467
Abstract

Embryonic stem cells can propagate indefinitely in a pluripotent state, able to differentiate into all types of specialized cells when restored to the embryo. What sustains their pluripotency during propagation remains unclear. Here, we show that core pluripotency factors OCT4 and SOX2 suppress chaperone-mediated Autophagy (CMA), a selective form of Autophagy, until the initiation of differentiation. Low CMA activity promotes embryonic stem cell self-renewal, whereas its up-regulation enhances differentiation. CMA degrades isocitrate dehydrogenases IDH1 and IDH2 and reduces levels of intracellular α-ketoglutarate, an obligatory cofactor for various histone and DNA demethylases involved in pluripotency. These findings suggest that CMA mediates the effect of core pluripotency factors on metabolism, shaping the epigenetic landscape of stem cells and governing the balance between self-renewal and differentiation.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-112483
    99.59%, CMA激活剂
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