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调节成体干细胞静止及其在维持组织完整性中的功能。

Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity.

机构信息

Department of Neurology and Neurological Science, Stanford University School of Medicine, Stanford, CA, USA.

Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.

出版信息

Nat Rev Mol Cell Biol. 2023 May;24(5):334-354. doi: 10.1038/s41580-022-00568-6. Epub 2023 Mar 15.

Abstract

Adult stem cells are important for mammalian tissues, where they act as a cell reserve that supports normal tissue turnover and can mount a regenerative response following acute injuries. Quiescent stem cells are well established in certain tissues, such as skeletal muscle, brain, and bone marrow. The quiescent state is actively controlled and is essential for long-term maintenance of stem cell pools. In this Review, we discuss the importance of maintaining a functional pool of quiescent adult stem cells, including haematopoietic stem cells, skeletal muscle stem cells, neural stem cells, hair follicle stem cells, and mesenchymal stem cells such as fibro-adipogenic progenitors, to ensure tissue maintenance and repair. We discuss the molecular mechanisms that regulate the entry into, maintenance of, and exit from the quiescent state in mice. Recent studies revealed that quiescent stem cells have a discordance between RNA and protein levels, indicating the importance of post-transcriptional mechanisms, such as alternative polyadenylation, alternative splicing, and translation repression, in the control of stem cell quiescence. Understanding how these mechanisms guide stem cell function during homeostasis and regeneration has important implications for regenerative medicine.

摘要

成体干细胞对于哺乳动物组织非常重要,它们充当细胞储备库,支持正常组织更新,并能在急性损伤后启动再生反应。静止的干细胞在某些组织中已经得到很好的证实,如骨骼肌、脑和骨髓。静止状态是被积极控制的,对于长期维持干细胞池是必不可少的。在这篇综述中,我们讨论了维持功能性静止的成体干细胞池的重要性,包括造血干细胞、骨骼肌干细胞、神经干细胞、毛囊干细胞和间充质干细胞(如成纤维脂肪祖细胞),以确保组织的维持和修复。我们讨论了调节小鼠进入、维持和退出静止状态的分子机制。最近的研究表明,静止的干细胞在 RNA 和蛋白质水平之间存在不一致性,这表明转录后机制(如可变多聚腺苷酸化、可变剪接和翻译抑制)在控制干细胞静止方面的重要性。了解这些机制如何指导干细胞在体内平衡和再生过程中的功能,对于再生医学具有重要意义。

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