Under normal physiological conditions, microglia are the only parenchymal cell type that originates outside the brain. They largely develop in the yolk sac, infiltrate the mouse brain at embryonic day 9.5, and include multiple subpopulations. In a study published in Immunity, Van Hove et al. describe an additional distinct subset.
The authors analyzed microglia populations in the brain’s circumventricular organs (CVOs), where the blood–brain barrier is less tight than in the inner-brain parenchyma. Pairing single-cell transcriptomics with lineage tracing, the authors uncovered previously unrecognized microglia subsets with mixed developmental origins. Specifically, CVO microglia are transcriptionally distinct from those in the rest of the brain, expressing higher levels of activation markers such as genes associated with IFN signaling.
Surprisingly, a substantial proportion of the microglia were derived from fetal monocytes that enter the CNO perinatally; depletion of these cells resulted in repopulation predominantly by resident, yolk-sac-derived microglia. The study thus expands our understanding of microglia niches and opens additional avenues for shifting microglia populations in specific regions of the brain. Original reference: Immunity https://doi.org/10.1016/j.immuni.2026.09.002 (2026) This is a preview of subscription content, access via your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription Receive 12 print issues and online access Prices may be subject to local taxes which are calculated during checkout Nature Neuroscience https://www.nature.com/neuro/ Marin, I.A.
A brain of many microglia origins. Nat Neurosci 29, 2625 (2026). https://doi.org/10.1038/s41593-026-02509-4 DOI: https://doi.org/10.1038/s41593-026-02509-4
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