ATG5 nonautophagically regulates inflammation and differentiation in mouse embryonic stem cells

Autophagy. 2024 Aug;20(8):1897-1898. doi: 10.1080/15548627.2024.2330042. Epub 2024 Mar 22.

Abstract

Embryonic stem cells (ESCs), with abilities of infinite proliferation (self-renewal) and to differentiate into distinct cell types (pluripotency), show attenuated inflammatory response against cytokines or pathogens, which is recognized as a unique characteristic of ESCs compared with somatic cells. However, the underlying molecular mechanisms remain unclear, and whether the attenuated inflammatory state is involved in ESC differentiation is completely unknown. Our recent study demonstrated that macroautophagy/autophagy-related protein ATG5 inhibits the inflammatory response of mouse ESCs (MmESCs) by promoting the degradation of BTRC/β-TrCP1 and further the downregulation of NFKB/NF-κB signaling. In addition, maintenance of an attenuated inflammation status in MmESCs is required for their differentiation. In conclusion, ATG5 is a key regulator for the regulation of inflammatory response and differentiation of MmESCs.

Keywords: ATG5; FBXW7; embryonic stem cells; inflammatory response; β-TrCP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein 5* / genetics
  • Autophagy-Related Protein 5* / metabolism
  • Cell Differentiation*
  • Inflammation* / pathology
  • Mice
  • Mouse Embryonic Stem Cells* / cytology
  • Mouse Embryonic Stem Cells* / metabolism
  • NF-kappa B / metabolism
  • Signal Transduction

Substances

  • Autophagy-Related Protein 5
  • Atg5 protein, mouse
  • NF-kappa B

Grants and funding

This work was supported by the National Natural Science Foundation of China [No.: 82273067 and 81972650] (to S.C.), the Natural Science Foundation of Henan Province [No.: 222300420028] (to S.C.), the Natural Science Foundation of Shandong Province [No.: ZR2021QC181] (to S.L.), and the China Postdoctoral Science Foundation [No.: 2023M730964] (to L.Y.).