title: C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages.
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.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hoeffel
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Jinmiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yonit
authors.initials: Y
authors.lastname: Lavin
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Donovan
authors.initials: D
authors.lastname: Low
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Francisca F
authors.initials: FF
authors.lastname: Almeida
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Peter
authors.initials: P
authors.lastname: See
authors.affiliation: Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California-Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Beaudin
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Josephine
authors.initials: J
authors.lastname: Lum
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Ivy
authors.initials: I
authors.lastname: Low
authors.affiliation: Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California-Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA.
authors.forename: E Camilla
authors.initials: EC
authors.lastname: Forsberg
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zolezzi
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Anis
authors.initials: A
authors.lastname: Larbi
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore.
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.affiliation: 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.
authors.forename: Jerry K Y
authors.initials: JK
authors.lastname: Chan
authors.affiliation: Institute of Experimental Immunology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Greter
authors.affiliation: Institute of Experimental Immunology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kai Yuan Avenue, Science Park, Guangzhou, 510530 China.
authors.forename: Igor M
authors.initials: IM
authors.lastname: Samokhvalov
authors.affiliation: 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.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648 Singapore. Electronic address: florent_ginhoux@immunol.a-star.edu.sg.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D058948:Cell Tracking; D004622:Embryo, Mammalian; D005260:Female; D005333:Fetus; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D007668:Kidney / Q000166:cytology / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy; D061251:Primary Cell Culture; D020598:Proto-Oncogene Proteins c-myb / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology; D015017:Yolk Sac / Q000166:cytology / Q000276:immunology
chemical_list: D015415:Biomarkers; D020598:Proto-Oncogene Proteins c-myb