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C-Myb+ Erythro-Myeloid Progenitor-Derived Fetal Monocytes Give Rise to Adult Tissue-Resident Macrophages
Open accessAbstract
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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“The transcription factors Spi1 and Irf8 have been shown to be the core orchestrators for microglia development”
From Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program (2019) · cites this paper as Hoeffel et al., 2015
Experimental — accuracy not yet measuredIn the citing paper
“consistent with microglia emerging from PU.1 and IRF8-dependent, but MYB-independent cells 34–37.”
From Efficient derivation of microglia-like cells from human pluripotent stem cells (2016) · cites this paper as [36]
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“…EMP-E/EMP-M: Kit , Myb , Cd34, Itga2b ), monocyte progenitors (MonoP: Irf8 , Csf1r ), LMP ( Flt3 , Il7r, Spi1 ), dendritic cell Chin Assoc of Blood Sci precursors (pre-DC: Cd74 , Ccr2 ), mast cell precursors (pre-MC: Cpa3 , Hdc ), and neutrophil precursors (pre-Neu: Elane , Cebpe ) 4,35–40 ( Fig.”
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In-Depth Proteomic Analysis Reveals Phenotypic Diversity of Macrophages in Liver Fibrosis
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Metadata
- Authors
- Hoeffel, G., Chen, J., Lavin, Y., Low, D., Almeida, F. F., See, P., Beaudin, A. E., Lum, J., Low, I., Forsberg, E. C., Poidinger, M., Zolezzi, F., Larbi, A., Ng, L. G., Chan, J. K. Y., Greter, M., Becher, B., Samokhvalov, I. M., Merad, M., & Ginhoux, F.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Tisch Cancer Institute (US)
- University of California, Santa Cruz (US)
- University of Zurich (CH)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Ginhoux, Florent
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 42
- Issue
- 4
- Pages
- 665-678
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4545768
- OpenAlex
- W2023666964
- Cited by
- 1,135
- References
- 55
- Citations by year
- 2026: 64 · 2025: 84 · 2024: 111 · 2023: 99 · 2022: 135 · 2021: 122 · 2020: 118 · 2019: 102 · 2018: 107 · 2017: 81 · 2016: 67 · 2015: 44
- FWCI
- 77.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- National University of Singapore (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL086899, R01HL086899)
- National Cancer Institute (R01CA173861, R01CA112100, CA112100, R01CA190400)
- National Institute of Allergy and Infectious Diseases (AI080884, R01AI080884)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100917)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- tissue-resident macrophages, erythro-myeloid progenitors, microglia, yolk sac hematopoiesis, fetal liver hematopoiesis, MYB, fate mapping
- MeSH terms
- Aging, Animals, Cell Differentiation, Embryo, Mammalian, Female, Fetus, Hematopoietic Stem Cells, Kidney, Liver, Lung, Macrophages, Monocytes, Pregnancy, Skin, Yolk Sac, Biomarkers, Microglia, Cell Lineage, Proto-Oncogene Proteins c-myb, Myeloid Progenitor Cells, Mice, Cell Tracking, Primary Cell Culture
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