A Subpopulation of Microglia Generated in the Adult Mouse Brain Originates from Prominin-1-Expressing Progenitors.

Autor:	Prater KE; Departments of Neurology and., Aloi MS; Departments of Neurology and.; Pathology, University of Washington, Seattle, Washington 98195., Pathan JL; Departments of Neurology and., Winston CN; Departments of Neurology and., Chernoff RA; Departments of Neurology and., Davidson S; Departments of Neurology and., Sadgrove M; Department of Neurology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599., McDonough A; Departments of Neurology and., Zierath D; Departments of Neurology and., Su W; Departments of Neurology and., Weinstein JR; Departments of Neurology and.; Center on Human Development and Disability, University of Washington, Seattle, Washington 98195., Garden GA; Departments of Neurology and gagarden@email.unc.edu.; Pathology, University of Washington, Seattle, Washington 98195.; Center on Human Development and Disability, University of Washington, Seattle, Washington 98195.; Department of Neurology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2021 Sep 22; Vol. 41 (38), pp. 7942-7953. Date of Electronic Publication: 2021 Aug 11.
DOI:	10.1523/JNEUROSCI.1893-20.2021
Abstrakt:	Microglia maintain brain health and play important roles in disease and injury. Despite the known ability of microglia to proliferate, the precise nature of the population or populations capable of generating new microglia in the adult brain remains controversial. We identified Prominin-1 (Prom1; also known as CD133) as a putative cell surface marker of committed brain myeloid progenitor cells. We demonstrate that Prom1-expressing cells isolated from mixed cortical cultures will generate new microglia in vitro To determine whether Prom1-expressing cells generate new microglia in vivo , we used tamoxifen inducible fate mapping in male and female mice. Induction of Cre recombinase activity at 10 weeks in Prom1-expressing cells leads to the expression of TdTomato in all Prom1-expressing progenitors and newly generated daughter cells. We observed a population of new TdTomato-expressing microglia at 6 months of age that increased in size at 9 months. When microglia proliferation was induced using a transient ischemia/reperfusion paradigm, little proliferation from the Prom1-expressing progenitors was observed with the majority of new microglia derived from Prom1-negative cells. Together, these findings reveal that Prom1-expressing myeloid progenitor cells contribute to the generation of new microglia both in vitro and in vivo Furthermore, these findings demonstrate the existence of an undifferentiated myeloid progenitor population in the adult mouse brain that expresses Prom1. We conclude that Prom1-expressing myeloid progenitors contribute to new microglia genesis in the uninjured brain but not in response to ischemia/reperfusion. SIGNIFICANCE STATEMENT Microglia, the innate immune cells of the CNS, can divide to slowly generate new microglia throughout life. Newly generated microglia may influence inflammatory responses to injury or neurodegeneration. However, the origins of the new microglia in the brain have been controversial. Our research demonstrates that some newly born microglia in a healthy brain are derived from cells that express the stem cell marker Prominin-1. This is the first time Prominin-1 cells are shown to generate microglia. (Copyright © 2021 the authors.)
Databáze:	MEDLINE
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