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端粒调控与干细胞多能性的关联。

Linking Telomere Regulation to Stem Cell Pluripotency.

机构信息

State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin 300071, China.

出版信息

Trends Genet. 2017 Jan;33(1):16-33. doi: 10.1016/j.tig.2016.10.007. Epub 2016 Nov 23.

Abstract

Embryonic stem cells (ESCs), somatic cell nuclear transfer ESCs, and induced pluripotent stem cells (iPSCs) represent the most studied group of PSCs. Unlimited self-renewal without incurring chromosomal instability and pluripotency are essential for the potential use of PSCs in regenerative therapy. Telomere length maintenance is critical for the unlimited self-renewal, pluripotency, and chromosomal stability of PSCs. While telomerase has a primary role in telomere maintenance, alternative lengthening of telomere pathways involving recombination and epigenetic modifications are also required for telomere length regulation, notably in mouse PSCs. Telomere rejuvenation is part of epigenetic reprogramming to pluripotency. Insights into telomere reprogramming and maintenance in PSCs may have implications for understanding of aging and tumorigenesis. Here, I discuss the link between telomere elongation and homeostasis to the acquisition and maintenance of stem cell pluripotency, and their regulatory mechanisms by epigenetic modifications.

摘要

胚胎干细胞(ESCs)、体细胞核移植胚胎干细胞和诱导多能干细胞(iPSCs)代表了最受研究关注的一组多能干细胞。多能干细胞在再生治疗中的潜在应用需要其具有无限自我更新能力而不发生染色体不稳定和多能性。端粒长度维持对于多能干细胞的无限自我更新、多能性和染色体稳定性至关重要。虽然端粒酶在端粒维持中起主要作用,但涉及重组和表观遗传修饰的替代性端粒延长途径也需要用于端粒长度调节,特别是在小鼠多能干细胞中。端粒的年轻化是多能性重编程的一部分。对多能干细胞中端粒重编程和维持的深入了解可能对理解衰老和肿瘤发生具有重要意义。在这里,我讨论了端粒伸长和动态平衡与干细胞多能性的获得和维持之间的联系,以及它们通过表观遗传修饰的调控机制。

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