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bioRxiv · 10.1101/2021.04.08.439077

Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific

Eddins, D. J.·Kosters, A.·Waters, J.·Sosa, J.·Phillips, M.·Yadava, K.·Herzenberg, L. A.·Kuipers, H. F.·Ghosn, E.
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Abstract

Tissue-resident macrophages (TRM{Phi}) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRM{Phi} have undergone intense scrutiny where now most TRM{Phi} 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 TRM{Phi}, but their requirement is tissue-specific.

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Eddins, D. J., Kosters, A., Waters, J., Sosa, J., Phillips, M., Yadava, K., Herzenberg, L. A., Kuipers, H. F., Ghosn, E.. 2021-04-10. Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific. https://doi.org/10.1101/2021.04.08.439077

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