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Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

Accepted version
Peer-reviewed

Type

Article

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Authors

Saçma, Mehmet 
Pospiech, Johannes 
Bogeska, Ruzhica 

Abstract

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.

Description

Keywords

Aging, Animals, Bone Marrow, Capillaries, Cell Differentiation, Cell Division, Cell Polarity, Cell Tracking, Doxycycline, Fluorouracil, Gene Expression Regulation, Genes, Reporter, Green Fluorescent Proteins, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Histones, Homeostasis, Jagged-2 Protein, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myeloablative Agonists, Stem Cell Niche

Journal Title

Nat Cell Biol

Conference Name

Journal ISSN

1465-7392
1476-4679

Volume Title

21

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Medical Research Council (MC_PC_12009)
European Research Council (648765)