Adipogenesis

STAT5

Biology

Molecular biology

Chemistry

In vitro

Signal transduction

Cell biology

Biochemistry

The FASEB Journal

Bone marrow stem cells (BMSCs) are multipotent stem cells that can regenerate mesenchymal tissues, such as adipose tissue, bone, and muscle. Recent studies have shown that N6-methyladenosine (m6A) methylation, one of the most prevalent epigenetic modifications, is involved in the development process. However, whether it plays roles in BMSC differentiation is still elusive. Here, we found that the deletion of m6A "writer" protein methyltransferase-like (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expression via an m6A-dependent way. Knockdown of METTL3 decreased mRNA m6A levels of JAK1, leading to enhanced YTH m6A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) β, which could ultimately lead to a modulated adipogenic process. Collectively, our results reveal an orchestrated network linking the m6A methylation and JAK1/STAT5/C/EBPβ pathway in pBMSCs adipogenic differentiation. Our findings provide novel insights into the underlying molecular mechanisms of m6A modification in the regulation of BMSCs differentiating into adipocytes, which may pave a way to develop more effective therapeutic strategies in stem cell regenerative medicine and the treatment of obesity.-Yao, Y., Bi, Z., Wu, R., Zhao, Y., Liu, Y., Liu, Q., Wang, Y., Wang, X. METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m6A-YTHDF2-dependent manner.

METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway <i>via</i> an m <sup>6</sup> A‐YTHDF2–dependent manner

METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m 6 A‐YTHDF2–dependent manner

METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m ⁶ A‐YTHDF2–dependent manner