Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals
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nihms809521.pdf
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Author(s)
Sawai, Catherine M.
Babovic, Sonja
Upadhaya, Samik
Knapp, David J.H.F.
Lavin, Yonit
Lau, Colleen M.
Feng, Jue
Fujisaki, Joji
Ding, Lei
Merad, Miriam
Date Issued
August 2016
Journal
Immunity
Publisher
Elsevier
Citation
Sawai, Catherine M. et al. “Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.” Immunity 45, 3 (September 2016): 597–609 © 2016 Elsevier Inc
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Physics
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.IMMUNI.2016.08.007
