Fate mapping analysis reveals that adult microglia derive from primitive macrophages.
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.
Department of Gene and Cell Medicine and the Immunology Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA. Florent_ginhoux@immunol.a-star.edu.sg
Florent
F
Ginhoux
Melanie
M
Greter
Marylene
M
Leboeuf
Sayan
S
Nandi
Peter
P
See
Solen
S
Gokhan
Mark F
MF
Mehler
Simon J
SJ
Conway
Lai Guan
LG
Ng
E Richard
ER
Stanley
Igor M
IM
Samokhvalov
Miriam
M
Merad
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000196:embryology; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D005260:Female; D055879:Gene Knock-In Techniques; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006706:Homeostasis; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology*; D023461:Myeloid Progenitor Cells / Q000166:cytology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015017:Yolk Sac / Q000166:cytology
D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor