Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

Nature cell biology 2019 Nov

filter terms:

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.

Citation

Mehmet Saçma, Johannes Pospiech, Ruzhica Bogeska, Walter de Back, Jan-Philipp Mallm, Vadim Sakk, Karin Soller, Gina Marka, Angelika Vollmer, Rebekah Karns, Nina Cabezas-Wallscheid, Andreas Trumpp, Simón Méndez-Ferrer, Michael D Milsom, Medhanie A Mulaw, Hartmut Geiger, Maria Carolina Florian. Haematopoietic stem cells in perisinusoidal niches are protected from ageing. Nature cell biology. 2019 Nov;21(11):1309-1320