Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages

By Florent Ginhoux, M. Greter, M. Leboeuf, Sayan Nandi, Peter See, Solen Gokhan, M. Mehler, S. Conway, Lai Guan Ng, E. Stanley and 2 more. Science, 2010

4,761 citations recorded by the source corpus.

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. The developmental origins of adult microglia are revealed. 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.

Subfields: Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/ca1f6780aab9a846b98ef72efe4edde3b6e5782a

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Citations in the corpus

Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis (2012, neutral): “This complication was recently clarified in a series of studies that aimed to define the origins of brain microglia (Ginhoux et al., 2010).”
Depression as a microglial disease. (2015, background): “The microglial progenitors migrate from the extraembryonic yolk sac into the developing CNS and disperse almost evenly throughout the entire brain [172].”
New tools for studying microglia in the mouse and human CNS (2016, background): “(2000) Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion.”
Microglia development follows a stepwise program to regulate brain homeostasis (2016, methodology): “To study the dynamics of the gene programs involved in microglia development, we performed RNA sequencing (RNA-seq) tomeasure the global gene expression of myeloid progenitors from the yolk sac (5) and microglia from embryonic, postnatal, and adult brains (36) for a total of nine time points through”
Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment (2014, background): “…demonstrated that most tissues are populated early during fetal development by macrophages that subsequently maintain themselves, independently of adult hematopoiesis, through longevity and limited self-renewal (Ginhoux et al., 2010; Hashimoto et al., 2013; Schulz et al., 2012; Yona et al., 2013).”
Tissue-specific signals control reversible program of localization and functional polarization of macrophages. (2014, positive): “Recent studies uncovered that a substantial portion of tissue macrophages arises from yolk sac during embryogenesis, and these cells are maintained by local proliferation (Ginhoux et al., 2010; Schulz et al., 2012).”
Repertoire of microglial and macrophage responses after spinal cord injury (2011, background): “Recent studies show that during development, microglial cells are derived from primitive myeloid progenitors in the yolk sa”