LncRNA NEAT1 controls the lineage fates of BMSCs during skeletal aging by impairing mitochondrial function and pluripotency maintenance.

ABSTRACT: Aged bone marrow mesenchymal stem cells (BMSCs) exhibit aberrant self-renewal and lineage specification, which contribute to imbalanced bone-fat and progressive bone loss. In addition to known master regulators of lineage commitment, it is crucial to identify pivotal switches governing the specific differentiation fate of aged BMSCs. Here, we profiled differences in epigenetic regulation between adipogenesis and osteogenesis and identified super-enhancer associated lncRNA nuclear-enriched abundant transcript 1 (NEAT1) as a key bone-fat switch in aged BMSCs. We validated that NEAT1 with high enhancer activity was transcriptionally activated by ATF2 and directed aged BMSCs to a greater propensity to differentiate toward adipocytes than osteoblasts by mediating mitochondrial function. Further

SUBMITTER: Zhang H 

PROVIDER: S-EPMC8816946 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature