CBFA2T2 promotes adipogenic differentiation of mesenchymal stem cells by regulating CEBPA

Biochem Biophys Res Commun. 2020 Aug 20;529(2):133-139. doi: 10.1016/j.bbrc.2020.05.120. Epub 2020 Jun 20.

Abstract

The unique metabolic characteristics and diverse functions of marrow adipose tissue (MAT) have drawn more attention recently. Previously, we have reported that CBFA2T2 is required for BMP2-induced osteogenic differentiation of mesenchymal stem/stromal cells (MSCs). In the present study, we further investigated the role of CBFA2T2 in regulation of adipogenic differentiation in mouse bone marrow-derived MSCs (mBMSCs) and human dental pulp stem cells (hDPSCs). We found CBFA2T2 expression was dramatically upregulated during adipogenesis of mBMSCs and hDPSCs. More importantly, knockdown of CBFA2T2 in mBMSCs and hDPSCs significantly inhibited the process of adipogenic differentiation, as revealed by the expression of adipogenic markers and Oil Red O staining. Mechanistically, we found knockdown of CBFA2T2 led to an increase in H3K9me2 and H3K9me3 levels at promoter of CEBPA, an essential transcription factor of adipogenesis. Taken together, these findings suggest CBFA2T2 is key regulator of adipogenic differentiation of MSCs, and it may represent a therapeutic target for conditions with excessive MAT.

Keywords: Adipogenesis; CBFA2T2; Histone methylation; Marrow adipose tissue; Stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis*
  • Adult
  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Cells, Cultured
  • Dental Pulp / cytology*
  • Dental Pulp / metabolism
  • Gene Knockdown Techniques
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Young Adult

Substances

  • CBFA2T2 myeloid-transforming gene-related protein
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • CEBPA protein, mouse
  • Repressor Proteins