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C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages.

Authors
  • Hoeffel, Guillaume1
  • Chen, Jinmiao1
  • Lavin, Yonit2
  • Low, Donovan1
  • Almeida, Francisca F1
  • See, Peter1
  • Beaudin, Anna E3
  • Lum, Josephine1
  • Low, Ivy1
  • Forsberg, E Camilla3
  • Poidinger, Michael1
  • Zolezzi, Francesca1
  • Larbi, Anis1
  • Ng, Lai Guan1
  • Chan, Jerry K Y4
  • Greter, Melanie5
  • Becher, Burkhard5
  • Samokhvalov, Igor M6
  • Merad, Miriam2
  • Ginhoux, Florent7
  • 1 Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore. , (Singapore)
  • 2 Department of Oncological Sciences, The Tisch Cancer Institute, 1425 Madison Avenue, New York, NY 10029, USA; The Immunology Institute, Icahn school of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
  • 3 Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California-Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA.
  • 4 Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore; Experimental Fetal Medicine Group, NUHS Tower Block level 12, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, 119228 Singapore; Reproductive Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899 Singapore; Singapore and Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, 169857 Singapore. , (Singapore)
  • 5 Institute of Experimental Immunology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. , (Switzerland)
  • 6 Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kai Yuan Avenue, Science Park, Guangzhou, 510530 China. , (China)
  • 7 Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore. Electronic address: [email protected] , (Singapore)
Type
Published Article
Journal
Immunity
Publication Date
Apr 21, 2015
Volume
42
Issue
4
Pages
665–678
Identifiers
DOI: 10.1016/j.immuni.2015.03.011
PMID: 25902481
Source
Medline
License
Unknown

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.

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