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Nat Cell Biol. 2019 Nov;21(11):1309-1320. doi: 10.1038/s41556-019-0418-y. Epub 2019 Nov 4.

Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

Author information

1
Institute of Molecular Medicine, Stem Cells and Aging, Aging Research Center, Ulm University, Ulm, Germany.
2
Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, Deutsches Krebsforschungszentrum, Division of Experimental Hematology, Heidelberg, Germany.
3
Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
4
Deutsches Krebsforschungszentrum, Division of Chromatin Network, Heidelberg, Germany.
5
Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, USA.
6
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
7
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Hematology, University of Cambridge, Cambridge, United Kingdom.
8
National Health Service Blood & Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
9
Molecular Oncology Institute of Experimental Cancer Research, Medical Faculty, University of Ulm, Ulm, Germany.
10
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, USA.
11
Institute of Molecular Medicine, Stem Cells and Aging, Aging Research Center, Ulm University, Ulm, Germany. carolina.florian@uni-ulm.de.
12
Center for Regenerative Medicine in Barcelona, Bellvitge Institute for Biomedical Research, Barcelona, Spain. carolina.florian@uni-ulm.de.

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.

PMID:
31685996
DOI:
10.1038/s41556-019-0418-y

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