Embryonic macrophages orchestrate niche cell homeostasis for the establishment of the definitive hematopoietic stem cell pool

Gülce Perçin (), Konstantin Riege, Julia Fröbel, Jonas Metz, Stephan Culemann, Mathias Lesche, Susanne Reinhardt, Thomas Höfer, Steve Hoffmann and Claudia Waskow ()
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Gülce Perçin: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Konstantin Riege: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Julia Fröbel: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Jonas Metz: German Cancer Research Center
Stephan Culemann: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Mathias Lesche: c/o CMCB Center for Molecular and Cellular Bioengineering Technology Platform of the TUD Dresden University of Technology
Susanne Reinhardt: c/o CMCB Center for Molecular and Cellular Bioengineering Technology Platform of the TUD Dresden University of Technology
Thomas Höfer: German Cancer Research Center
Steve Hoffmann: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Claudia Waskow: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Embryonic macrophages emerge before the onset of definitive hematopoiesis, seed into discrete tissues and contribute to specialized resident macrophages throughout life. Presence of embryonic macrophages in the bone marrow and functional impact on hematopoietic stem cells (HSC) or the niche remains unclear. Here we show that bone marrow macrophages consist of two ontogenetically distinct cell populations from embryonic and adult origin. Newborn mice lacking embryonic macrophages have decreased HSC numbers in the bone marrow suggesting an important function for embryo-derived macrophages in orchestrating HSC trafficking around birth. The establishment of a normal cellular niche space in the bone marrow critically depends on embryonic macrophages that are important for the development of mesenchymal stromal cells, but not other non-hematopoietic niche cells, providing evidence for a specific role for embryo-derived macrophages in the establishment of the niche environment pivotal for the establishment of a normally sized HSC pool.

Date: 2025
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DOI: 10.1038/s41467-025-59059-9

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