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Abstract
Pluripotent stem cells (PSCs) hold great promise in cell-based therapy because of their pluripotent property and the ability to proliferate indefinitely. Embryonic stem cells (ESCs) derived from inner cell mass (ICM) possess unique cell cycle control with shortened G1 phase. In addition, ESCs have high expression of homologous recombination (HR)-related proteins, which repair double-strand breaks (DSBs) through HR or the non-homologous end joining (NHEJ) pathway. On the other hand, the generation of induced pluripotent stem cells (iPSCs) by forced expression of transcription factors (Oct4, Sox2, Klf4, c-Myc) is accompanied by oxidative stress and DNA damage. The DNA repair mechanism of DSBs is therefore critical in determining the genomic stability and efficiency of iPSCs generation. Maintaining genomic stability in PSCs plays a pivotal role in the proliferation and pluripotency of PSCs. In terms of therapeutic application, genomic stability is the key to reducing the risks of cancer development due to abnormal cell replication. Over the years, we and other groups have identified important regulators of DNA damage response in PSCs, including FOXM1, SIRT1 and PUMA. They function through transcription regulation of downstream targets (P53, CDK1) that are involved in cell cycle regulations. Here, we review the fundamental links between the PSC-specific HR process and DNA damage response, with a focus on the roles of FOXM1 and SIRT1 on maintaining genomic integrity.
Highlights
Embryonic stem cells (ESCs) of mice [1] or humans [2] are derived from the inner cell mass (ICM) of blastocysts
In 2006, Yamanaka and his team reported the generation of induced pluripotent stem cells from mouse embryonic and adult fibroblasts through induction of transcription factors (Oct4, Sox2, Klf4 and c-Myc) [10]
Another major difference between mouse ESCs (mESCs) and human ESCs (hESCs) is that the expression pattern of the cyclin A/E–CDK2 complex is cell cycle dependent in hESCs, but it is constant in mESCs
Summary
Embryonic stem cells (ESCs) of mice [1] or humans [2] are derived from the ICM of blastocysts They hold great promise in cell-based therapy because of their pluripotent nature and the ability to proliferate indefinitely. Understanding the biological characteristics of pluripotent stem cells (PSCs) is imperative for exploring their potential applications Both ESCs and iPSCs can proliferate rapidly. The mitotic cell division is the most fundamental process for all cell types It is tightly regulated by the activation and deactivation of cyclin-dependent kinases (CDK) and the oscillatory expression of cyclins at different stages of the cell cycle. It was found that the mouse embryonic cells have rapid cell divisions with doubling time of 5–10 h, owing to the shortened and truncated G1 and G2 phases [23]
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