Haematopoietic stem cells in perisinusoidal niches are protected from ageing.
Milsom, Michael D
Nat Cell Biol
Springer Science and Business Media LLC
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Saçma, M., Pospiech, J., Bogeska, R., de Back, W., Mallm, J., Sakk, V., Soller, K., et al. (2019). Haematopoietic stem cells in perisinusoidal niches are protected from ageing.. Nat Cell Biol, 21 (11), 1309-1320. https://doi.org/10.1038/s41556-019-0418-y
With ageing, intrinsic haematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing also affects the HSC niche, and thereby impairs its capacity to support HSC function, is still widely debated. Here, by using in-vivo long-term label-retention assays we demonstrate that aged label-retaining HSCs, which are, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches are uniquely preserved in shape, morphology and number on ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches in the long term, which is linked to the lack of recovery of endothelial Jag2 at sinusoids. Overall, our data characterize the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and thereby protect HSCs from ageing.
Capillaries, Hematopoietic Stem Cells, Bone Marrow, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Fluorouracil, Doxycycline, Green Fluorescent Proteins, Histones, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Cell Division, Cell Differentiation, Cell Polarity, Gene Expression Regulation, Aging, Homeostasis, Genes, Reporter, Stem Cell Niche, Cell Tracking, Jagged-2 Protein
Medical Research Council (MC_PC_12009)
European Research Council (648765)
External DOI: https://doi.org/10.1038/s41556-019-0418-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/298974
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