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Science 330 (6005): 841-845

Copyright © 2010 by the American Association for the Advancement of Science

Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages

Florent Ginhoux,1,2,* Melanie Greter,1 Marylene Leboeuf,1 Sayan Nandi,3 Peter See,2 Solen Gokhan,4 Mark F. Mehler,4,5 Simon J. Conway,6 Lai Guan Ng,2 E. Richard Stanley,3 Igor M. Samokhvalov,7 Miriam Merad1,*

Abstract: Microglia are the resident macrophages of the central nervous system and are associated with the pathogenesis of many neurodegenerative and brain inflammatory diseases; however, the origin of adult microglia remains controversial. We show that postnatal hematopoietic progenitors do not significantly contribute to microglia homeostasis in the adult brain. In contrast to many macrophage populations, we show that microglia develop in mice that lack colony stimulating factor-1 (CSF-1) but are absent in CSF-1 receptor–deficient mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors that arise before embryonic day 8. These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.

1 Department of Gene and Cell Medicine and the Immunology Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
2 Singapore Immunology Network (SIgN), 8A Biomedical Grove, IMMUNOS Building Nos. 3-4, BIOPOLIS, 138648, Singapore.
3 Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
4 Institute for Brain Disorders and Neural Regeneration, Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, and Department of Neurology, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY 10461, USA.
5 Departments of Neuroscience, Psychiatry, and Behavioral Sciences, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY 10461, USA.
6 Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202, USA.
7 Laboratory for Stem Cell Biology, Center for Developmental Biology (CDB), RIKEN Kobe, Kobe 6500047, Japan.

* To whom correspondence should be addressed. E-mail: Miriam.Merad{at}mssm.edu (M.M.); Florent_ginhoux{at}immunol.a-star.edu.sg (F.G.)

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