Knockdown of MBD3 Promotes Pluripotency and In Vitro Differentiation Ability of Bovine iPSCs by Reducing DNA Damage via HIF1A During Reprogramming

The DNA damage response (DDR) is susceptible to occurrence during the reprogram-ming process induced by Yamanaka factors, which constrains the generation and ap-plication of induced pluripotent stem cells (iPSCs). The present study demonstrates that the knockdown (KD) of MBD3, a member of the nucleosome remodeling and deacetylase (NuRD) complex, reduced DDR during the early stages of bovine somatic cell re-programming, and enhanced pluripotency and in vitro differentiation ability of bovine iPSCs. MBD3 KD reduced the generation of reactive oxygen species (ROS) by upregulated of HIF1A expression, which mitigate DNA damage and apoptosis induced by oxidative stress in bovine iPSCs. Conversely, the overexpression of MBD3 increased DNA damage throughout the reprogramming process. In conclusion, our results demonstrate that the knockdown of MBD3 during reprogramming can reduce DNA damage and promote the generation of bovine iPSCs with enhanced pluripotency and in vitro differentiation ability.