A subpopulation of embryonic microglia respond to maternal stress and influence nearby neural progenitors

• Published in: Developmental cell Vol. 56; no. 9; pp. 1326 - 1345.e6
• Main Authors: Rosin, Jessica M., Sinha, Sarthak, Biernaskie, Jeff, Kurrasch, Deborah M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.05.2021
• Subjects: development; embryogenesis; hypothalamus; microglia; neural progenitors; stress; transcriptional profiling; stress; transcriptional profiling; development; embryogenesis; neural progenitors; microglia; hypothalamus
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2021.03.018

The interplay between hypothalamic neurons and microglia as they integrate stressors to regulate homeostasis is of growing interest. We asked if microglia in the embryonic hypothalamus were likewise stress responsive and, if so, whether their precocious activation perturbs nearby neural stem cell (NSC) programs. We performed single-cell transcriptomics to define embryonic hypothalamic microglia heterogeneity and identified four microglial subsets, including a subpopulation adjacent to NSCs that was responsive to gestational cold stress. Stress exposure elevated CCL3 and CCL4 secretion, but only in male brains, and ex vivo CCL4 treatment of hypothalamic NSCs altered proliferation and differentiation. Concomitantly, gestational stress decreased PVN oxytocin neurons only in male embryos, which was reversed by microglia depletion. Adult offspring exposed to gestational stress displayed altered social behaviors, which was likewise microglia dependent, but only in males. Collectively, immature hypothalamic microglia play an unappreciated role in translating maternal stressors to sexually dimorphic perturbation of neurodevelopmental programs. [Display omitted] •Embryonic hypothalamic microglia are heterogeneous•A subpopulation of embryonic hypothalamic microglia reside adjacent to NSCs•Maternal cold stress impacts embryonic microglia signaling to nearby NSCs in males•Exposure to gestational stress leads to disrupted social behaviors in adulthood Rosin et al. show that the embryonic hypothalamus is comprised of four unique microglial subpopulations, including one microglial cluster that responds to maternal cold stress and influence nearby NSCs in a sexually dimorphic manner, suggesting that maturing microglia play an unappreciated role in translating maternal stressors to perturbations in neurodevelopment.