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Immunity. 2016 Sep 20;45(3):597-609. doi: 10.1016/j.immuni.2016.08.007. Epub 2016 Aug 30.

Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.

Author information

1
Department of Pathology, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: catherine.sawai@nyumc.org.
2
Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 4E6, Canada.
3
Department of Pathology, New York University Langone Medical Center, New York, NY 10016, USA; Graduate Program in Pathobiology and Molecular Medicine, Columbia University Medical Center, New York, NY 10032, USA.
4
Department of Oncological Science, The Tisch Cancer Institute and The Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
5
Department of Pathology, New York University Langone Medical Center, New York, NY 10016, USA.
6
Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
7
Department of Pediatrics and Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
8
Department of Regenerative Medicine and Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
9
Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
10
Department of Pathology, New York University Langone Medical Center, New York, NY 10016, USA; Department of Medicine, New York University Langone Medical Center, New York, NY 10016, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: boris.reizis@nyumc.org.

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.

PMID:
27590115
PMCID:
PMC5054720
DOI:
10.1016/j.immuni.2016.08.007
[Indexed for MEDLINE]
Free PMC Article

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