C-Myb(+) Erythro-Myeloid Progenitor-Derived Fetal Monocytes Give Rise to Adult Tissue-Resident Macrophages

Immunity. 2015 Apr 21;42(4):665-78. doi: 10.1016/j.immuni.2015.03.011.

Abstract

Although classified as hematopoietic cells, tissue-resident macrophages (MFs) arise from embryonic precursors that seed the tissues prior to birth to generate a self-renewing population, which is maintained independently of adult hematopoiesis. Here we reveal the identity of these embryonic precursors using an in utero MF-depletion strategy and fate-mapping of yolk sac (YS) and fetal liver (FL) hematopoiesis. We show that YS MFs are the main precursors of microglia, while most other MFs derive from fetal monocytes (MOs). Both YS MFs and fetal MOs arise from erythro-myeloid progenitors (EMPs) generated in the YS. In the YS, EMPs gave rise to MFs without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal MOs that then seeded embryonic tissues and differentiated into MFs. Thus, adult tissue-resident MFs established from hematopoietic stem cell-independent embryonic precursors arise from two distinct developmental programs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Lineage / immunology
  • Cell Tracking
  • Embryo, Mammalian
  • Female
  • Fetus
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Kidney / cytology
  • Kidney / immunology
  • Liver / cytology
  • Liver / immunology
  • Lung / cytology
  • Lung / immunology
  • Macrophages / cytology
  • Macrophages / immunology*
  • Mice
  • Microglia / cytology
  • Microglia / immunology
  • Monocytes / cytology
  • Monocytes / immunology*
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / immunology*
  • Pregnancy
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-myb / immunology*
  • Proto-Oncogene Proteins c-myb / metabolism
  • Skin / cytology
  • Skin / immunology
  • Yolk Sac / cytology
  • Yolk Sac / immunology

Substances

  • Biomarkers
  • Proto-Oncogene Proteins c-myb

Associated data

  • GEO/GSE66970