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Early-wave macrophages control late hematopoiesis

Sara Monticelli1, Alina Sommer2, Zeinab AlHajj Hassan1

  • 1IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67400 Illkirch, France; Centre National de la Recherche Scientifique, UMR 7104, 67400 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, UMR, S 1258, 67400 Illkirch, France; Université de Strasbourg, IGBMC UMR 7104- UMR-S 1258, 67400 Illkirch, France.

Developmental Cell
|April 3, 2024
PubMed

Insights

Early-wave macrophages (EMs) are crucial for organ development. Removing EMs accelerates late hematopoiesis in mice and Drosophila by influencing extracellular matrix, not inflammation.

Area of Science:

  • Immunology
  • Developmental Biology
  • Hematopoiesis

Background:

  • Macrophages are key immune cells, but their role in organ development and homeostasis is increasingly recognized.
  • Early-wave macrophages (EMs), originating independently of hematopoietic stem cells (HSCs), establish the fetal liver niche essential for HSC expansion and differentiation.
  • Niche defects are implicated in myeloid malignancies, prompting investigation into HSC regulatory cues.

Purpose of the Study:

  • To investigate the role of evolutionarily conserved early-wave macrophages (EMs) in modulating late hematopoiesis.
  • To determine if EMs influence hematopoietic stem cells (HSCs) through mechanisms beyond inflammation or phagocytosis.

Main Methods:

  • Comparative analysis of EMs in Drosophila and mouse models.
  • Assessment of late hematopoiesis rates in the absence of EMs.
  • Investigation of the correlation between EMs, inflammation, and macrophage phagocytic activity.
  • Analysis of extracellular matrix components derived from EMs.

Main Results:

  • Loss of EMs in both Drosophila and mice led to accelerated late hematopoiesis.
  • This acceleration was independent of inflammatory responses and macrophage phagocytic capabilities.
  • Extracellular matrix components produced by EMs were identified as key factors driving the acceleration of late hematopoiesis.

Conclusions:

  • Early-wave macrophages (EMs) play a significant, previously unappreciated developmental role in regulating hematopoiesis.
  • EMs modulate late hematopoiesis through their secreted extracellular matrix components, rather than inflammatory or phagocytic functions.
  • This finding highlights a novel mechanism by which immune cells contribute to organ development and tissue homeostasis.
Keywords:
developmentevolutionextracellular matrixhematopoietic stem cellshematopoietic waveshemocytesimmune developmentlymph glandmacrophagesontogeny

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