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Updated: Jun 7, 2026
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Fate mapping analysis reveals that adult microglia derive from primitive macrophages
Florent Ginhoux1, Melanie Greter, Marylene Leboeuf
1Department 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
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.
Insights
Adult microglia originate from early embryonic myeloid progenitors, not postnatal blood cells. This discovery clarifies the unique origin of these crucial brain immune cells.
Area of Science:
- Neuroimmunology
- Developmental neuroscience
- Hematopoiesis
Background:
- Microglia, the central nervous system's resident macrophages, are implicated in neurodegenerative and inflammatory brain diseases.
- The precise origin and developmental trajectory of adult microglia have remained a subject of scientific debate.
- Understanding microglial origins is critical for developing targeted therapies for neurological disorders.
Purpose of the Study:
- To elucidate the developmental origin of microglia in the adult central nervous system.
- To determine the contribution of postnatal hematopoietic progenitors to microglial homeostasis.
- To investigate the role of colony-stimulating factor-1 (CSF-1) and its receptor in microglial development.
Main Methods:
- Utilized genetically modified mice lacking colony-stimulating factor-1 (CSF-1) or its receptor.
- Conducted in vivo lineage tracing studies starting from early embryonic stages (before embryonic day 8).
- Assessed the contribution of postnatal hematopoietic progenitors to adult microglial populations.
Main Results:
- Postnatal hematopoietic progenitors do not significantly contribute to the maintenance of microglia in the adult brain.
- Microglia develop in the absence of CSF-1 but are absent in mice lacking the CSF-1 receptor, highlighting the receptor's essential role.
- Lineage tracing confirmed that adult microglia are derived from primitive myeloid progenitors originating before embryonic day 8.
Conclusions:
- Adult microglia represent an ontogenically distinct population within the broader mononuclear phagocyte system.
- Microglia originate from early embryonic progenitors, independent of postnatal hematopoiesis.
- These findings have significant implications for utilizing embryonically derived microglial progenitors in therapeutic strategies for brain disorders.
