Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Primitive Origins for Microglia
Microglia are the resident macrophages of the central nervous system and are associated with neurodegeneration and brain inflammatory diseases. Although the developmental origins of other tissue macrophage populations are well established, the origins of microglia remain controversial. Ginhoux et al. (p. 841, published online 21 October) used in vivo lineage tracing studies to show that microglia arise early in mouse development and derive from primitive macrophages in the yolk sac. This is in contrast to other cells of the mononuclear phagocyte system, which arise later in development from a distinct progenitor population.
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.
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Science
Volume 330 | Issue 6005
5 November 2010
5 November 2010
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Copyright © 2010, American Association for the Advancement of Science.
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Submission history
Received: 6 July 2010
Accepted: 7 October 2010
Published in print: 5 November 2010
Acknowledgments
We thank S. Nishikawa, H. Snoeck, and P. S. Frenette for intellectual input in the study; the RIKEN CDB Laboratory for Animal Resources and Genetic Engineering for providing the Runx1-MER-Cre-MER mice; G. Hoeffel, X. H. Zong, R. Basu and H. Ketchum for technical assistance; and L. Robinson for critical review and editing of the manuscript. This work was supported by NIH grants CA112100, HL086899, and AI080884 to M.M.; CA32551 and CA26504 to E.R.S.; and MH66290 and NS38902 to M.M. I.M.S. is supported by a grant from RIKEN Strategic Programs for Research and Development (President’s Fund). M.G. is supported by the National Science Foundation of Switzerland. Runx1-MER-Cre-MER mice have CDB accession. no. CDB0524K (www.cdb.riken.jp/arg/mutant%20mice%20list.html).
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