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Stress-Induced Changes in Bone Marrow Stromal Cell Populations Revealed through Single-Cell Protein Expression Mapping
Abstract
Summary: Stromal cell populations that maintain hematopoietic stem and progenitor cells (HSPCs) are generally characterized in steady-state conditions. Here we report a comprehensive atlas of bone marrow stromal cell subpopulations under homeostatic and stress conditions using mass cytometry (CyTOF)-based single-cell protein analysis. We identified 28 subsets of nonhematopoietic cells during homeostasis, 14 of which expressed hematopoietic regulatory factors. Irradiation-based conditioning for HSPC transplantation led to the loss of most of these populations, including the LeptinR+ and Nestin+ subsets. In contrast, a subset expressing Ecto-5’-Nucleotidase (CD73) was retained and a specific CD73+NGFR(hi) population expresses high levels of cytokines during homeostasis and stress. Genetic ablation of CD73 compromised HSPC transplantation in an acute setting without long-term changes in bone marrow HSPCs. Thus, this protein-based expression mapping reveals distinct sets of stromal cells in the bone marrow and how they change in clinically-relevant stress settings to contribute to early stages of hematopoietic regeneration.
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“Because irradiation can influence the processes that control clonal hematopoiesis and its cardiovascular impact by damaging the bone marrow niche and heart”
From Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction (2020) · cites this paper as [19]
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Metadata
- Authors
- Severe, N., Karabacak, N. M., Gustafsson, K., Baryawno, N., Courties, G., Kfoury, Y., Kokkaliaris, K. D., Rhee, C., Lee, D., Scadden, E. W., Garcia-Robledo, J. E., Brouse, T., Nahrendorf, M., Toner, M., & Scadden, D. T.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 25
- Issue
- 4
- Pages
- 570-583.e7
- ISSN
- 1934-5909
- PMC
- PMC6778015
- Cited by
- 130
- References
- 41
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 368 d)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (EB012493)
- Novartis
- Shriners Hospitals for Children (84070)
- Philippe Foundation
- National Institutes of Health (EB002503)
- Agios Pharmaceuticals
- National Cancer Institute (CA163191)
- Fondation pour la Recherche Médicale
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