PAX7 Balances the Cell Cycle Progression via Regulating Expression of Dnmt3b and Apobec2 in Differentiating PSCs

Cells. 2021 Aug 26;10(9):2205. doi: 10.3390/cells10092205.

Abstract

PAX7 transcription factor plays a crucial role in embryonic myogenesis and in adult muscles in which it secures proper function of satellite cells, including regulation of their self renewal. PAX7 downregulation is necessary for the myogenic differentiation of satellite cells induced after muscle damage, what is prerequisite step for regeneration. Using differentiating pluripotent stem cells we documented that the absence of functional PAX7 facilitates proliferation. Such action is executed by the modulation of the expression of two proteins involved in the DNA methylation, i.e., Dnmt3b and Apobec2. Increase in Dnmt3b expression led to the downregulation of the CDK inhibitors and facilitated cell cycle progression. Changes in Apobec2 expression, on the other hand, differently impacted proliferation/differentiation balance, depending on the experimental model used.

Keywords: 5azaC; ESCs; Pax7; cell cycle; differentiation; iPSCs; mouse; myogenesis; skeletal muscle; stem cells; teratoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC Deaminases / genetics
  • APOBEC Deaminases / metabolism*
  • Animals
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • DNA Methylation
  • DNA Methyltransferase 3B
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Development / genetics
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism*
  • PAX7 Transcription Factor / physiology
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / physiology
  • Satellite Cells, Skeletal Muscle / metabolism

Substances

  • Cell Cycle Proteins
  • Muscle Proteins
  • PAX7 Transcription Factor
  • Pax7 protein, mouse
  • DNA (Cytosine-5-)-Methyltransferases
  • APOBEC Deaminases
  • Apobec2 protein, mouse