The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging
Open accessPublished version of a preprint
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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 the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907
A Direct Measurement of the Radiation Sensitivity of Normal Mouse Bone Marrow Cells1
Till, J. E., & McCulloch, E. A. (2010) · Radiation Research · doi:10.1667/rrxx28.1 · Cited by 4,036
A Direct Measurement of the Radiation Sensitivity of Normal Mouse Bone Marrow Cells
Till, J. E., & McCulloch, E. A. (1961) · Radiation Research · doi:10.2307/3570892 · Cited by 3,848
Kiel, M. J., Yilmaz, Ö. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005) · Cell · doi:10.1016/j.cell.2005.05.026 · Cited by 3,168
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617
Wilson, A., Laurenti, E., Oser, G., van der Wath, R. C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C. F., Eshkind, L., Bockamp, E., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.048 · Cited by 1,908
Tissue-Resident Macrophage Ontogeny and Homeostasis
Ginhoux, F., & Guilliams, M. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.024 · Cited by 1,884
Identification of Flt3+ Lympho-Myeloid Stem Cells Lacking Erythro-Megakaryocytic Potential
Adolfsson, J., Månsson, R., Buza-Vidas, N., Hultquist, A., Liuba, K., Jensen, C. T., Bryder, D., Yang, L., Borge, O. J., Thorén, L., et al. (2005) · Cell · doi:10.1016/j.cell.2005.02.013 · Cited by 1,323
Self-citationCell intrinsic alterations underlie hematopoietic stem cell aging
Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503280102 · Cited by 1,152 · cited 2×
“Together with an overall decline in multilineage HSC contribution of aged mice, these results strongly propose a model in which aging associates with reduced/compromised HSC differentiation, which in combination with the well-established expansion of HSCs with age (Morrison et al., 1996; Rossi et al., 2005; Sudo et al…”
BackgroundSelf-citationTranscriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors
Paul, F., Arkin, Y., Giladi, A., Jaitin, D. A., Kenigsberg, E., Keren-Shaul, H., Winter, D., Lara-Astiaso, D., Gury, M., Weiner, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.013 · Cited by 1,082
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–120 of 120
IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustionPreprint
Aldridge, D. L., Lanzar, Z. R., Phan, A. T., Christian, D. A., Pardy, R. D., Min, B., Kedl, R. M., & Hunter, C. A. (2025) · eLife · doi:10.7554/elife.105876.2 · Cited by 1
Leukemia stem cell expansion cultures reveal clonal drivers of leukemogenesis and therapy responsePreprint
Singh, I., Polazzi, A., Pombo, A. M., López-Osias, M., Bauer, C., Guarini, M., Sánchez-Sánchez, P., Goulet, L., Gallardo, C., Fernández-Pérez, D., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.24.707683 · Cited by 1
Characterising the role of Zeb1 in the adult haematopoietic system
Almotiri, A. (2019) · ORCA Online Research @Cardiff (Cardiff University)
Investigating increased hematopoietic stem cell fitness in a novel mouse model
Karra, L., & Roose, J. P. (2021) · Small GTPases · doi:10.1080/21541248.2021.1882832
Immature Myeloid Cell Deposition in Old Bone Marrow Revealed by Single-Cell Transcriptome AnalysisPreprint
Kim, W.-J., Kim, K., Moon, J.-I., Park, S. G., Cho, Y., Kim, H. J., Shin, H., Yoon, H., & Ryoo, H. (2022) · Research Square · doi:10.1101/2022.10.15.512392
Zhang, Q., Olofzon, R., Konturek-Cieśla, A., Yuan, O., & Bryder, D. (2024) · eLife · doi:10.7554/elife.91826.2
Self-citationThe transcription factor Bcl11a is essential for functional B-1a cell maintenance during agingPreprint
Yu, Y., Xu, S., Huang, L., Zhang, L., Wang, J., Hu, Y., Yang, Y., Shi, X., Liu, C., Wang, R., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4825323/v1
Protocol to induce cell labeling in vivo and to trace labeled hematopoietic cells using mouse models
Syed, A., Kobayashi, M., & Yoshimoto, M. (2024) · STAR Protocols · doi:10.1016/j.xpro.2024.103408
Clonal analysis of murine HSC self-renewal and differentiation in native hematopoiesisPreprint
You, C., Zhang, Z., Lin, L., & Sun, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.22.624575
STOCHASTIC MODELING OF HEMATOPOIETIC STEM CELL DYNAMICSPreprint
Alfaro-Quinde, C., Krstanovic, K. E., Vásquez, P. A., & Kathrein, K. L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.27.635091
Clonal analysis of murine HSC self-renewal and differentiation in native hematopoiesisPreprint
You, C., Zhang, Z., Lin, L., & Sun, J. (2025) · eLife · doi:10.7554/elife.104537
IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustionPreprint
Aldridge, D. L., Lanzar, Z. R., Phan, A. T., Christian, D. A., Pardy, R. D., Min, B., Kedl, R. M., & Hunter, C. A. (2025) · eLife · doi:10.7554/elife.105876.1
Zhang, Z., Jin, B., You, C., Li, Y., Lin, L., & Sun, J. (2026) · Developmental Cell · doi:10.1016/j.devcel.2026.02.003 · Cited by 1
Cell differentiation, stem cell regulation and impact of the mutations : a stochastic approach
Bonnet, C. (2020) · theses.fr (ABES) · doi:10.70675/f4280114z717cz4049z8b50ze5d948ae4801
Quantifying Haematopoietic Cell Dynamics
Hustin, L. (2022) · theses.fr (ABES) · doi:10.70675/48546646z0fa0z4e9bzb5a0zb1067f26721d
Suzuki, H., Miyachi, H., Yamada, N., Nishikawa, H., Kuno, S., Endoh, H., Shiina, T., Yoshikawa, R., Uemura, S., Iwama, A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.03.736310
Hematopoietic Stem Cell Metabolism during Stress and Aging
Sharma, D., & Filippi, M. (2026) · Advances in Geriatric Medicine and Research · doi:10.20900/agmr20260018
Metadata
- 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
- 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, 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
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 ›
Are you an author, or do you see a problem with this page? Request a review