Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging
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Abstract
A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.
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Direct fluorescent labeling of mouse HSCs under steady state conditions illustrated a significant and continued contribution of HSCs to nearly all steady state hematopoiesis.
“Similarly, direct fluorescent labeling of mouse HSCs under steady state conditions illustrated a significant and continued contribution of HSCs to nearly all steady state hematopoiesis (Chapple et al., 2018; Sawai et al., 2016; Säwen et al., 2018).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Säwen et al., 2018
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 [25]
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- Authors
- Säwen, P., Eldeeb, M., Erlandsson, E., Kristiansen, T. A., Laterza, C., Kokaia, Z., Karlsson, G., Yuan, J., Soneji, S., Mandal, P. K., Rossi, D. J., & Bryder, D.
- Affiliations
- Division of Molecular Hematology, Department of Laboratory Medicine, Medical Faculty, Lund University, Lund, Sweden
- Lund University (SE)
- Boston Children's Hospital (US)
- Corresponding author
- Bryder, David
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-12-18
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6298771
- OpenAlex
- W2904698165
- Cited by
- 120
- References
- 56
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 16 · 2023: 16 · 2022: 19 · 2021: 13 · 2020: 19 · 2019: 10
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Cancerfonden
- The Tobias foundation (Tobias Prize)
- Vetenskapsrådet
- Knut och Alice Wallenbergs Stiftelse
- European Research Council (ERC Consolidator grant (615068))
- 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, multilineage hematopoiesis, HSC aging, hematopoietic progenitor cells, HSC expansion
- MeSH terms
- Age Factors, Aging, Animals, Cell Differentiation, Hematopoiesis, Hematopoietic Stem Cells, Staining and Labeling, Cell Lineage, Mice
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