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生物物理因素在干细胞不对称分裂中的调控作用。

Biophysical factors in the regulation of asymmetric division of stem cells.

机构信息

Centre for Healthcare Science and Technology, Indian Institute of Engineering Science and Technology, Shibpur, Howrah, West Bengal 711103, India.

出版信息

Biol Rev Camb Philos Soc. 2019 Jun;94(3):810-827. doi: 10.1111/brv.12479. Epub 2018 Nov 22.

Abstract

Stem cells are a promising cell source for regenerative medicine due to their characteristics of self-renewal and differentiation. The intricate balance between these two cell fates is maintained by precisely controlled symmetric and asymmetric cell divisions. Asymmetric division has a fundamental importance in maintaining tissue homeostasis and in the development of multi-cellular organisms. For example, during development, asymmetric cell divisions are responsible for the formation of the body axis. Mechanistically, mitotic spindle dynamics determine the assembly and separation of chromosomes and regulate the orientation of cell division. Interestingly, symmetric and asymmetric cell division is not mutually exclusive and a range of factors are involved in such cell-fate decisions, the measurement of which can provide efficient and reliable information on the regenerative potential of a cell. The balance between self-renewal and differentiation in stem cells is controlled by various biophysical and biochemical cues. Although the role of biochemical factors in asymmetric stem cell division has been widely studied, the effect of biophysical cues in stem-cell self-renewal is not comprehensively understood. Herein, we review the biological relevance of stem-cell asymmetric division to regenerative medicine and discuss the influences of various intrinsic and extrinsic biophysical cues in stem-cell self-renewal. This review particularly aims to inform the clinical translation of efforts to control the self-renewal ability of stem cells through the tuning of various biophysical cues.

摘要

干细胞因其自我更新和分化的特性,成为再生医学有前途的细胞来源。这两种细胞命运之间的精细平衡是通过精确控制对称和不对称细胞分裂来维持的。不对称分裂对于维持组织内稳态和多细胞生物的发育具有根本重要性。例如,在发育过程中,不对称细胞分裂负责形成身体轴。从机制上讲,有丝分裂纺锤体动力学决定了染色体的组装和分离,并调节细胞分裂的方向。有趣的是,对称和不对称细胞分裂并非相互排斥,一系列因素参与了这种细胞命运决定,对这些因素的测量可以提供有关细胞再生潜力的有效且可靠的信息。干细胞中自我更新和分化之间的平衡受各种生物物理和生化线索的控制。尽管生物化学因素在不对称干细胞分裂中的作用已被广泛研究,但生物物理线索在干细胞自我更新中的作用尚未得到全面理解。在此,我们回顾了干细胞不对称分裂对再生医学的生物学相关性,并讨论了各种内在和外在生物物理线索对干细胞自我更新的影响。本综述特别旨在告知通过调整各种生物物理线索来控制干细胞自我更新能力的临床转化。

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