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Haematopoietic stem cells in perisinusoidal niches are protected from ageing
Open accessAbstract
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.
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“Likewise, in bone marrow from old mice, a pool of quiescent HSCs located close to sinusoids (FIG. 1b) may be protected from some ageing effects38.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [38]
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Self-citation
Metadata
- Authors
- Saçma, M., Pospiech, J., Bogeska, R., de Back, W., Mallm, J.-P., Sakk, V., Soller, K., Marka, G., Vollmer, A., Karns, R., Cabezas-Wallscheid, N., Trumpp, A., Méndez-Ferrer, S., Milsom, M. D., Mulaw, M. A., Geiger, H., & Florian, M. C.
- Affiliations
- Universität Ulm (DE)
- German Cancer Research Center (DE)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Florian, Maria Carolina
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2019-11
- Volume
- 21
- Issue
- 11
- Pages
- 1309-1320
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2986117925
- Cited by
- 133
- References
- 81
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 18 · 2023: 23 · 2022: 19 · 2021: 26 · 2020: 21 · 2019: 2
- FWCI
- 12.10
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Deutsche Forschungsgemeinschaft (FL 921/1-1, FOR2674, SFB1074)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Keywords
- hematopoietic stem cells, aging, HSC quiescence, myeloablative chemotherapy, bone marrow microenvironment
- MeSH terms
- Jagged-2 Protein, Aging, Animals, Bone Marrow, Capillaries, Cell Differentiation, Cell Division, Doxycycline, Fluorouracil, Gene Expression Regulation, Hematopoietic Stem Cells, Histones, Homeostasis, Mice, Inbred C57BL, Mice, Transgenic, Cell Polarity, Genes, Reporter, Hematopoietic Stem Cell Transplantation, Myeloablative Agonists, Green Fluorescent Proteins, Mice, Stem Cell Niche, Cell Tracking
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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