Graduate Student University of Tsukuba Tsukuba, Ibaraki, Japan
Abstract: Induced pluripotent stem cells (iPSCs) are critical for disease modeling and drug development, yet the mechanisms driving pluripotency induction are not fully resolved. We have found that PARK7 (DJ-1), a regulator of oxidative stress and transcription, promotes differentiation in mouse embryonic stem cells (mESCs) and hinders somatic cell reprogramming, though its precise role remains unclear. We investigated PARK7’s function during pluripotency induction in low-KLF4 (LowK) paused iPSCs, a stable partially reprogrammed iPSCs. Park7 knockdown (KD) in LowK paused iPSCs upregulated the expression of pluripotency markers (Nanog and Rex1) and increased glycolysis through an increase in reactive oxygen species (ROS) and HIF1α stabilization. In contrast, PARK7 overexpression (OE) at an early stage of somatic cell reprogramming suppressed these markers but enhanced them at a later stage, revealing reprogramming stage-specific effects. These findings suggest PARK7 inhibits early pluripotency induction by limiting ROS and HIF1α-driven glycolysis yet aids later stages. This dual role elucidates PARK7’s impact on reprogramming efficiency, offering insights into optimizing iPSC generation for therapeutic applications and understanding pluripotency dynamics.
