AUTHOR=Hu Alexander J. , Li Wei , Pathak Apana , Hu Guo-Fu , Hou Xiaoli , Farmer Stephen R. , Hu Miaofen G. 

TITLE=CDK6 is essential for mesenchymal stem cell proliferation and adipocyte differentiation

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1146047

DOI=10.3389/fmolb.2023.1146047

ISSN=2296-889X

ABSTRACT=Overweight or obesity is a risk of many obesity-related metabolic diseases. Among all the potential new therapies, stem cell-based treatments hold great promise for treating many obesity-related metabolic diseases. However, the mechanisms regulating adipocyte stem cells / progenitors (precursors) are unknown.  In the current study, we found that mice with a kinase-inactive cyclin-dependent kinase 6 (CDK6) mutants (K43M) had fewer precursor residents in the stromal-vascular fraction (SVF) of adult white adipose tissue (WAT). Adipocyte-derived stem cells (ADSCs) from the SVF or mouse embryonic fibroblasts (MEFs) from K43M mice had defects in proliferation and differentiation into the functional fat cells. In contrast, mice with a constitutively active kinase CDK6 mutant (R31C) had the opposite traits. Ablation of RUNX1 in both mature and precursor K43M cells, reversed the phenotypes. These results represent a novel role of CDK6 in regulating precursor numbers, proliferation, and differentiation, suggesting a potential pharmacological intervention for using CDK6 inhibitors in the treatment of obesity-related metabolic diseases.