Primitive macrophages control HSPC mobilization and definitive haematopoiesis

Nat Commun. 2015 Feb 17;6:6227. doi: 10.1038/ncomms7227.

Abstract

In vertebrates, haematopoietic stem/progenitor cells (HSPCs) first emerge in the aorta-gonad-mesonephros (AGM) before colonizing transitory and subsequently definitive haematopoietic organs allowing haematopoiesis throughout adult life. Here we identify an unexpected primitive macrophage population accumulated in the dorsal mesenteric mesoderm surrounding the dorsal aorta of the human embryo and study its function in the transparent zebrafish embryo. Our study reveals dynamic interactions occurring between the HSPCs and primitive macrophages in the AGM. Specific chemical and inducible genetic depletion of macrophages or inhibition of matrix metalloproteinases (Mmps) leads to an accumulation of HSPCs in the AGM and a decrease in the colonization of haematopoietic organs. Finally, in vivo zymography demonstrates the function of primitive macrophages in extracellular matrix degradation, which allows HSPC migration through the AGM stroma, their intravasation, leading to the colonization of haematopoietic organs and the establishment of definitive haematopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Aorta / embryology*
  • Cell Lineage
  • Developmental Biology
  • Extracellular Matrix / metabolism
  • Gonads / embryology
  • Hematopoiesis*
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mesonephros / embryology
  • Microscopy, Fluorescence
  • Stem Cells / cytology*
  • Zebrafish

Substances

  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • MMP9 protein, human
  • Matrix Metalloproteinase 9