RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells

	RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells
	Cai, WZ; Yao, XQ; Liu, GJ; Liu, XY; Zhao, B; Shi, P
	2024
发表期刊	CELLULAR AND MOLECULAR LIFE SCIENCES
ISSN	1420-682X
卷号	81 期号:1
摘要	Background Chromosome stability is crucial for homeostasis of pluripotent stem cells (PSCs) and early-stage embryonic development. Chromosomal defects may raise carcinogenic risks in regenerative medicine when using PSCs as original materials. However, the detailed mechanism regarding PSCs chromosome stability maintenance is not fully understood. Methods Mouse embryonic stem cells (line D3) and human embryonic stem cells (line H9) were cultured under standard conditions. To confirm the loading of RetSat protein on mitotic chromosomes of PSCs, immunostaining was performed in PSCs spontaneous differentiation assay and iPSC reprogramming assay from mouse embryonic fibroblasts (MEFs), respectively. In addition, qPCR, immunoprecipitation, LC-MS/MS and immunoblotting were used to study the expression of RetSat, and interactions of RetSat with cohesin/condensin components. RNA sequencing and teratoma formation assay was conducted to evaluate the carcinogenic risk of mouse embryonic stem cells with RetSat deletion. Results We reported a PSC high-expressing gene, RetSat, plays key roles in chromosome stabilization. We identified RetSat protein localizing onto mitotic chromosomes specifically in stemness positive cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We found dramatic chromosome instability, e.g. chromosome bridging, lagging and interphase micronuclei in mouse and human ESCs when down regulating RetSat. RetSat knock-out mouse ESCs upregulated cancer associated gene pathways, and displayed higher tumorigenic capacities in teratoma formation assay. Mechanistically, we confirmed that RetSat interacts with cohesin/condensin components Smc1a and Nudcd2. RetSat deletion impaired the chromosome loading dosage of Smc1a, Smc3 and Nudcd2. Conclusions In summary, we reported RetSat to be a key stabilizer of chromosome condensation in pluripotent stem cells. This highlights the crucial roles of RetSat in early-stage embryonic development, and potential value of RetSat as an effective biomarker for assessing the quality of pluripotent stem cells.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14473
专题	科研部门_基因组稳定调控（赵博）
推荐引用方式 GB/T 7714	Cai, WZ,Yao, XQ,Liu, GJ,et al. RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells[J]. CELLULAR AND MOLECULAR LIFE SCIENCES,2024,81(1).
APA	Cai, WZ,Yao, XQ,Liu, GJ,Liu, XY,Zhao, B,&Shi, P.(2024).RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells.CELLULAR AND MOLECULAR LIFE SCIENCES,81(1).
MLA	Cai, WZ,et al."RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells".CELLULAR AND MOLECULAR LIFE SCIENCES 81.1(2024).

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