Niche stiffness underlies the ageing of central nervous system progenitor cells

Segel M, Neumann B, Hill MFE, Weber IP, Viscomi C, Zhao C, Young A, Agley CC, Thompson AJ, Gonzalez GA, Sharma A, Holmqvist S, Rowitch DH, Franze K, Franklin RJM, Chalut KJ (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Nature Research

Book Volume: 573

Pages Range: 130-134

Journal Issue: 7772

DOI: 10.1038/s41586-019-1484-9

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 ‘niche’—a set of cell-extrinsic cues that include chemical and mechanical signals^3,4. 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.

Authors with CRIS profile

Kristian Franze

Involved external institutions

University of Cambridge

United Kingdom (GB)

How to cite

APA:

Segel, M., Neumann, B., Hill, M.F.E., Weber, I.P., Viscomi, C., Zhao, C.,... Chalut, K.J. (2019). Niche stiffness underlies the ageing of central nervous system progenitor cells. Nature, 573(7772), 130-134. https://doi.org/10.1038/s41586-019-1484-9

MLA:

Segel, Michael, et al. "Niche stiffness underlies the ageing of central nervous system progenitor cells." Nature 573.7772 (2019): 130-134.

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