Biology subjects

Viguier, S.

Publications and source records attributed to Viguier, S..

3 recordsLinked to original sources

bioRxiv2025

Epigenetic control of microglial developmental milestones from proliferative progenitors to efficient phagocytes

Early immune perturbations increase the risk of neurodegenerative and neurodevelopmental disorders, yet the mechanisms underlying the maturation of microglia, the resident immune cells of the brain parenchyma, remain poorly defined. Specifically, how proliferation, morphological differentiation, and phagocytosis are coordinated among microglia progenitors as they colonize the embryonic brain remains unclear. Here, we combined mathematical modeling with spatiotemporal analyses of the murine hippocampus and cerebellum from postnatal day 2 (P2) to P60 to reconstruct the trajectory of microglial development. We identified a proliferative-to-quiescent (P/Q) switch around P3/P4 that preceded the acquisition of morphological complexity and efficient phagocytosis and was accompanied by coordinated shifts in cell-cycle dynamics and metabolic state. Strikingly, this P/Q switch was recapitulated in repopulation contexts in mice and in the human fetal brain, where later stages displayed enhanced phagocytic function coupled to reduced proliferation. Perturbing the proliferative phase through pharmacological or genetic disruption of CSF1R signaling impaired subsequent microglial complexity and phagocytosis efficiency, revealing an unexpected reliance of phagocytosis on proliferation-driven colonization. Finally, we show that microglia stepwise maturation during development is associated with chromatin remodeling and driven by the epigenetic regulator Ikaros. Together, these findings uncover the sequential milestones of microglial development, revealing a potential period of early vulnerability and establishing an unexpected linkage between proliferation and phagocytosis essential to understanding how these processes are coordinated in neurodegenerative disorders.

neuroscience↗

bioRxiv2022

Hunter-gatherer oral microbiomes are shaped by contact network structure

Ancestral humans evolved a complex social structure still observed in extant hunter-gatherers. Here we investigate the effects of extensive sociality and mobility on the oral microbiome of 138 Agta hunter-gatherers from the Philippines. Comparisons of microbiome composition showed that the Agta are more similar to Central African Bayaka hunter-gatherers than to neighboring farmers. We also defined the Agta social microbiome as a set of 137 oral bacteria (only 7% of 1980 amplicon sequence variants) significantly influenced by social contact (quantified through wireless sensors of short-range interactions). We show that interaction networks covering large areas, and their strong links between close kin, spouses, and even unrelated friends, can significantly predict bacterial transmission networks across Agta camps. Finally, more central individuals to social networks are also bacterial supersharers. We conclude that hunter-gatherer social microbiomes, which are predominantly pathogenic, were shaped by evolutionary tradeoffs between extensive sociality and disease spread.

microbiology↗

bioRxiv2022

The making of the oral microbiome in Agta hunter-gatherers

Ecological and genetic factors have influenced the composition of the human microbiome during our evolutionary history. We analyzed the oral microbiota of the Agta, a hunter-gatherer population where part of its members is adopting an agricultural diet. We show that age is the strongest factor modulating the microbiome, likely through immunosenescence as there is an increase of pathogenicity with age. Biological and cultural processes generate sexual dimorphism in the oral microbiome. A small subset of oral bacteria is influenced by the host genome, linking host collagen genes to bacterial biofilm formation. Our data also suggests that shifting from a fish/meat to a rice-rich diet transforms their microbiome, mirroring the Neolithic transition. All these factors have implications in the epidemiology of oral diseases. Thus, the human oral microbiome is multifactorial, and shaped by various ecological and social factors that modify the oral environment.

microbiology↗