Limited rejuvenation of aged hematopoietic stem cells in young bone marrow niche
Open accessAbstract
Hematopoietic stem cells (HSCs) exhibit functional alterations, such as reduced regenerative capacity and myeloid-biased differentiation, with age. The HSC niche, which is essential for the maintenance of HSCs, also undergoes marked changes with aging. However, it has been technically challenging to directly evaluate the contribution of niche aging to age-associated HSC alterations without niche-damaging myeloablation in HSC transplantation assays. We herein transplanted an excess of aged HSCs into young mice without preconditioning. Although aged HSCs successfully engrafted in the intact young bone marrow niche, they poorly regenerated downstream progenitors and exhibited persistent myeloid-biased differentiation, resulting in no significant functional rejuvenation. Transcriptome and methylome analyses revealed that the young niche largely restored the transcriptional profile of aged HSCs, but not their DNA methylation profiles. Therefore, the restoration of the young niche is insufficient for rejuvenating HSC functions, highlighting a key role for age-associated cell-intrinsic defects in HSC aging.
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Extrinsic signals from old niches appear to dominate over intrinsic function of young stem cells in transplantation experiments, whereas signals from young niches may have only limited rejuvenation effects on old stem cells, at least for HSCs.
“Extrinsic signals from old niches appear to dominate over intrinsic function of young stem cells in transplantation experiments143,144. By contrast, signals from young niches may have only limited rejuvenation effects on old stem cells, at least for HSCs145.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [145]
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References 40 · Cited by 111
- Authors
- Kuribayashi, W., Oshima, M., Itokawa, N., Koide, S., Nakajima-Takagi, Y., Yamashita, M., Yamazaki, S., Rahmutulla, B., Miura, F., Ito, T., Kaneda, A., & Iwama, A.
- Affiliations
- Chiba University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan 2
- University of Tsukuba (JP)
- Kyushu University (JP)
- Corresponding author
- Iwama, Atsushi
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2020-11-24
- Volume
- 218
- Issue
- 3
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC7690939
- OpenAlex
- W3110162347
- Cited by
- 111
- References
- 40
- Citations by year
- 2026: 21 · 2025: 23 · 2024: 20 · 2023: 27 · 2022: 11 · 2021: 9
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (JP19H05653, JP26115002, JP19H05746)
- Japan Agency for Medical Research and Development (JP20am0101103)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- hematopoietic stem cells, HSC aging, bone marrow microenvironment, HSC transplantation, DNA methylation, transcriptional reprogramming, hematopoietic regeneration
- MeSH terms
- Aging, Animals, Bone Marrow, Hematopoiesis, Hematopoietic Stem Cells, Mice, Inbred C57BL, Rejuvenation, Transcription, Genetic, Cellular Senescence, DNA Methylation, Mice, Stem Cell Niche, Transcriptome
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