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PICH facilitates iPSC reprogramming by alleviating genomic instability induced by DNA replication stress
Fengjiao Zhang1, Chaoran Ji1, Fang Ji1
1Department of Pharmacy, Center for Regeneration and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Zhejiang-Denmark Joint Laboratory of Regeneration and Aging Medicine, Yiwu, China.
The FEBS Journal
|April 14, 2026
Summary
Plk1-interacting checkpoint helicase (PICH) maintains genomic stability during induced pluripotent stem cell (iPSC) reprogramming. Enhancing PICH levels boosts iPSC generation efficiency by reducing replication stress.
Area of Science:
- Stem cell biology
- Genomic stability
- Regenerative medicine
Background:
- Induced pluripotent stem cells (iPSCs) offer potential for tissue repair.
- Reprogramming efficiency is limited by challenges like DNA replication stress.
- Genomic instability during reprogramming reduces iPSC generation.
Purpose of the Study:
- To investigate the role of Plk1-interacting checkpoint helicase (PICH) in iPSC reprogramming.
- To determine if PICH can improve iPSC generation efficiency.
Main Methods:
- Studied PICH deficiency effects on iPSC generation.
- Assessed the impact of PICH overexpression on reprogramming efficiency.
- Investigated PICH's interaction with RIF1 in maintaining genomic stability.
Main Results:
- PICH deficiency led to genomic instability and reduced iPSC generation.
- PICH overexpression improved iPSC reprogramming efficiency by alleviating replication stress.
- PICH collaborates with RIF1 to maintain genomic stability in iPSCs.
Conclusions:
- PICH plays a crucial role in maintaining genomic stability during iPSC reprogramming.
- PICH facilitates iPSC generation by mitigating replication stress.
- Modulating PICH offers a novel strategy to enhance iPSC reprogramming efficiency.
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