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Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific

Devon J. Eddins, Astrid Kosters, Jeffrey Waters, Jasmine Sosa, Megan Phillips, Koshika Yadava, Leonore A. Herzenberg, Hedwich F. Kuipers, View ORCID ProfileEliver Eid Bou Ghosn
doi: https://doi.org/10.1101/2021.04.08.439077
Devon J. Eddins
*Lowance Center for Human Immunology, Department of Medicine, Division of Immunology and Rheumatology, Emory University School of Medicine, Atlanta, GA 30322, USA
†Department of Pediatrics, Division of Rheumatology, Emory University School of Medicine, Atlanta, GA 30322, USA
‡Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA
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Astrid Kosters
*Lowance Center for Human Immunology, Department of Medicine, Division of Immunology and Rheumatology, Emory University School of Medicine, Atlanta, GA 30322, USA
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Jeffrey Waters
§Department of Genetics, Stanford University, Stanford, CA 94305, USA
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Jasmine Sosa
§Department of Genetics, Stanford University, Stanford, CA 94305, USA
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Megan Phillips
§Department of Genetics, Stanford University, Stanford, CA 94305, USA
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Koshika Yadava
¶Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
∥Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, 4058 Basel, Switzerland
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Leonore A. Herzenberg
§Department of Genetics, Stanford University, Stanford, CA 94305, USA
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Hedwich F. Kuipers
¶Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
#Departments of Clinical Neurosciences and Cell Biology & Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
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Eliver Eid Bou Ghosn
*Lowance Center for Human Immunology, Department of Medicine, Division of Immunology and Rheumatology, Emory University School of Medicine, Atlanta, GA 30322, USA
†Department of Pediatrics, Division of Rheumatology, Emory University School of Medicine, Atlanta, GA 30322, USA
‡Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA
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  • ORCID record for Eliver Eid Bou Ghosn
  • For correspondence: eliver.ghosn@emory.edu
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Abstract

Tissue-resident macrophages (TRMΦ) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRMΦ have undergone intense scrutiny where now most TRMΦ are thought to originate early during embryonic development independent of hematopoietic stem cells (HSCs). We previously characterized two distinct subsets of mouse peritoneal cavity macrophages (Large and Small Peritoneal Macrophages; LPM and SPM, respectively) whose origins and relationship to both fetal and adult long-term (LT)-HSCs have not been fully investigated. Here we employ highly purified LT-HSC transplantation and in vivo lineage tracing to show a dual ontogeny for LPM and SPM, where the initial wave of peritoneal macrophages is seeded from yolk sac-derived precursors, which later require LT-HSCs for regeneration. In contrast, transplanted fetal and adult LT-HSCs are not able to regenerate brain-resident microglia. Thus, we demonstrate that LT-HSCs retain the potential to develop into TRMΦ, but their requirement is tissue-specific.

Competing Interest Statement

The authors have declared no competing interest.

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Posted April 10, 2021.
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Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific
Devon J. Eddins, Astrid Kosters, Jeffrey Waters, Jasmine Sosa, Megan Phillips, Koshika Yadava, Leonore A. Herzenberg, Hedwich F. Kuipers, Eliver Eid Bou Ghosn
bioRxiv 2021.04.08.439077; doi: https://doi.org/10.1101/2021.04.08.439077
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Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific
Devon J. Eddins, Astrid Kosters, Jeffrey Waters, Jasmine Sosa, Megan Phillips, Koshika Yadava, Leonore A. Herzenberg, Hedwich F. Kuipers, Eliver Eid Bou Ghosn
bioRxiv 2021.04.08.439077; doi: https://doi.org/10.1101/2021.04.08.439077

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