Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment
Open accessAbstract
Aging is linked to functional deterioration and hematological diseases. The hematopoietic system is maintained by hematopoietic stem cells (HSCs), and dysfunction within the HSC compartment is thought to be a key mechanism underlying age-related hematopoietic perturbations. Using single-cell transplantation assays with five blood-lineage analysis, we previously identified myeloid-restricted repopulating progenitors (MyRPs) within the phenotypic HSC compartment in young mice. Here, we determined the age-related functional changes to the HSC compartment using over 400 single-cell transplantation assays. Notably, MyRP frequency increased dramatically with age, while multipotent HSCs expanded modestly within the bone marrow. We also identified a subset of functional cells that were myeloid restricted in primary recipients but displayed multipotent (five blood-lineage) output in secondary recipients. We have termed this cell type latent-HSCs, which appear exclusive to the aged HSC compartment. These results question the traditional dogma of HSC aging and our current approaches to assay and define HSCs.
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Some HSCs become more poised towards myeloid progenitors during ageing.
“Similarly, some HSCs become more poised towards myeloid progenitors during ageing26.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [26]
In blood, lineage tracing, single-cell RNA-seq and large-scale clonal analysis studies indicate that old HSCs generate fewer lymphoid cells and are skewed towards the myeloid lineage.
“In blood, lineage tracing, single-cell RNA-seq and large-scale clonal analysis studies all indicate that old HSCs generate fewer lymphoid cells and are skewed towards the myeloid lineage23–26.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [26]
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References 22 · Cited by 202
- Authors
- Yamamoto, R., Wilkinson, A. C., Ooehara, J., Lan, X., Lai, C.-Y., Nakauchi, Y., Pritchard, J. K., & Nakauchi, H.
- Affiliations
- Stanford Medicine (US)
- Institute of Medical Science, The University of Tokyo (JP)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Nakauchi, Hiromitsu
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 22
- Issue
- 4
- Pages
- 600-607.e4
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC5896201
- OpenAlex
- W2795993938
- Cited by
- 202
- References
- 22
- Citations by year
- 2026: 14 · 2025: 30 · 2024: 22 · 2023: 28 · 2022: 25 · 2021: 24 · 2020: 26 · 2019: 26 · 2018: 7
- FWCI
- 14.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- JSPS
- CIRM (LA1_C12-06917)
- Uehara Memorial Foundation
- Siebel Scholars
- NIH (HG009431)
- Glenn Foundation
- Howard Hughes Medical Institute
- Bloodwise Visiting Fellow (15050)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- hematopoietic stem cells, HSC aging, single-cell transplantation, clonal analysis, bone marrow
- MeSH terms
- Aging, Animals, Hematopoietic Stem Cells, Hematopoietic Stem Cell Transplantation, Mice
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