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微环境僵硬是祖细胞衰老的原因
作者:小柯机器人 发布时间:2019/9/5 14:03:58

英国剑桥大学Kevin J. Chalut和Robin J. M. Franklin等研究人员合作发现,微环境僵硬是中枢神经系统祖细胞衰老的原因。这一研究成果于2019年9月5日发表在国际学术期刊《自然》上。

研究人员发现少突胶质细胞祖细胞(OPC)微环境随着年龄的增长而变硬,并且这种机械变化足以引起与年龄相关的OPC功能丧失。使用生物和合成的支架模拟年轻大脑的硬度,研究人员发现在这些支架上培养的分离老化OPC在分子和功能上恢复活力。当研究人员破坏机械信号传导时,OPC的增殖和分化率增加。研究人员将机械响应离子通道PIEZO1鉴定为OPC机械信号的关键介导者。抑制PIEZO1在体内能够无视机械信号并允许OPC在衰老的中枢神经系统(CNS)中维持活性。研究人员还发现PIEZO1在CNS发育过程中对调节细胞数量很重要。因此,这项研究表明组织硬度是OPC衰老的关键调节因子,并提供了成人干细胞和祖细胞功能随年龄变化的见解。这些研究结果不仅对于再生治疗的发展很重要,而且对于理解衰老过程本身也很重要。

据悉,由于成体干细胞和祖细胞群体的功能丧失,衰老使得组织再生减少。一个例子是广泛和丰富的中枢神经系统(CNS)多能干细胞(又称为少突胶质细胞祖细胞)群体的再生能力的降低。这种功能丧失的一个相对被忽视的潜在来源是干细胞“微环境”——一种细胞外的因素,包括化学和机械信号。

附:英文原文

Title: Niche stiffness underlies the ageing of central nervous system progenitor cells

Author: Michael Segel, Bjrn Neumann, Myfanwy F. E. Hill, Isabell P. Weber, Carlo Viscomi, Chao Zhao, Adam Young, Chibeza C. Agley, Amelia J. Thompson, Ginez A. Gonzalez, Amar Sharma, Staffan Holmqvist, David H. Rowitch, Kristian Franze, Robin J. M. Franklin, Kevin J. Chalut

Issue&Volume: Volume 573 Issue 7772

Abstract: Ageing causes a decline in tissue regeneration owing to a loss of function of adult stem cell and progenitor cell populations1. One example is the deterioration of the regenerative capacity of the widespread and abundant population of central nervous system (CNS) multipotent stem cells known as oligodendrocyte progenitor cells (OPCs)2. A relatively overlooked potential source of this loss of function is the stem cell nichea set of cell-extrinsic cues that include chemical and mechanical signals3,4. Here we show that the OPC microenvironment stiffens with age, and that this mechanical change is sufficient to cause age-related loss of function of OPCs. Using biological and synthetic scaffolds to mimic the stiffness of young brains, we find that isolated aged OPCs cultured on these scaffolds are molecularly and functionally rejuvenated. When we disrupt mechanical signalling, the proliferation and differentiation rates of OPCs are increased. We identify the mechanoresponsive ion channel PIEZO1 as a key mediator of OPC mechanical signalling. Inhibiting PIEZO1 overrides mechanical signals in vivo and allows OPCs to maintain activity in the ageing CNS. We also show that PIEZO1 is important in regulating cell number during CNS development. Thus we show that tissue stiffness is a crucial regulator of ageing in OPCs, and provide insights into how the function of adult stem and progenitor cells changes with age. Our findings could be important not only for the development of regenerative therapies, but also for understanding the ageing process itself.

DOI: 10.1038/s41586-019-1484-9

Source:https://www.nature.com/articles/s41586-019-1484-9

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html