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Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals
Open accessAbstract
Hematopoietic stem cells (HSCs) sustain long-term reconstitution of hematopoiesis in transplantation recipients, yet their role in the endogenous steady-state hematopoiesis remains unclear. In particular, recent studies suggested that HSCs provide a relatively minor contribution to immune cell development in adults. We directed transgene expression in a fraction of HSCs that maintained reconstituting activity during serial transplantations. Inducible genetic labeling showed that transgene-expressing HSCs gave rise to other phenotypic HSCs, confirming their top position in the differentiation hierarchy. The labeled HSCs rapidly contributed to committed progenitors of all lineages and to mature myeloid cells and lymphocytes, but not to B-1a cells or tissue macrophages. Importantly, labeled HSCs gave rise to more than two-thirds of all myeloid cells and platelets in adult mice, and this contribution could be accelerated by an induced interferon response. Thus, classically defined HSCs maintain immune cell development in the steady state and during systemic cytokine responses.
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“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 Sawai et al., 2016
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Cites
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InfluentialIFNα activates dormant haematopoietic stem cells in vivo
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Sorted by citations
Diversity, Mechanisms, and Significance of Macrophage Plasticity
Locati, M., Curtale, G., & Mantovani, A. (2020) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012718 · Cited by 2,199
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BackgroundHaematopoietic stem cell activity and interactions with the niche
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Developmental and Functional Heterogeneity of Monocytes
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BackgroundFrom haematopoietic stem cells to complex differentiation landscapes
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Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly
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Metadata
- Authors
- Sawai, C. M., Babovic, S., Upadhaya, S., Knapp, D. J. H. F., Lavin, Y., Lau, C. M., Goloborodko, A., Feng, J., Fujisaki, J., Ding, L., Mirny, L. A., Merad, M., Eaves, C. J., & Reizis, B.
- Affiliations
- NYU Langone Health (US)
- BC Cancer Agency (CA)
- Columbia University Irving Medical Center (US)
- Tisch Cancer Institute (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Sawai, Catherine M.
- Reizis, Boris
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 45
- Issue
- 3
- Pages
- 597-609
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC5054720
- OpenAlex
- W2517782886
- Cited by
- 381
- References
- 50
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 33 · 2023: 35 · 2022: 45 · 2021: 36 · 2020: 55 · 2019: 54 · 2018: 49 · 2017: 33 · 2016: 6
- FWCI
- 45.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute on Aging (R01AG049074)
- National Heart, Lung, and Blood Institute (R21HL113678, R01HL132074, R01HL129506)
- National Cancer Institute (R01CA173861, R01CA190400, R01CA154947, P30CA016087)
- National Institute of General Medical Sciences (T32GM008224)
- National Institute of Allergy and Infectious Diseases (R01AI072571, R21AI115382, T32AI100853, R37AI072571)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD055165)
- 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, steady-state hematopoiesis, myeloid cell development, lymphocyte development, megakaryopoiesis, interferon response, serial transplantation, B-1a cells, tissue macrophages
- MeSH terms
- Animals, B-Lymphocytes, Blood Platelets, Cell Differentiation, Hematopoiesis, Hematopoietic Stem Cells, Interferons, Macrophages, Mice, Inbred C57BL, Hematopoietic Stem Cell Transplantation, Cell Lineage, Myeloid Cells, Mice
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