Epigenomic states of microglia driving central nervous system repair in humans

Our goal is to understand the extrinsic and intrinsic determinants that shape microglia phenotypes and central nervous system (CNS) repair during homeostasis and neurologic diseases.

The adult human CNS comprises two germinal niches: the subgranular layer of the dentate gyrus in the hippocampus gives rise to neuronal cells, while neural stem cells (NSC) within the subventricular zone (SVZ) can differentiate into neuronal and glial cells. SVZ-derived progenitors migrate out of the SVZ and can engage in cellular regeneration
1. Such cellular dynamics are tightly regulated, yet may fail, leading to uncontrolled proliferation of NSCs or insufficient repair. Within this realm, microglia display a key regulatory component of the SVZ as they can sense injury, react to changes in the local microenvironment, and provide niche supporting factors that control NSC cellular dynamics
2–4. SVZ microglia comprises a molecularly and functionally distinct class of microglia with distinct morphology and marker expression patterns, which are absent in non-germinal niches such as the prefrontal cortex
5. However, in the human brain, local and peripheral cues and downstream mechanisms that determine microglia states and their efficacy to engage in CNS regeneration are not well understood.

Our goal is to investigate how the interaction of microglia with the region-specific microenvironment impacts epigenomic heterogeneity and microglia-induced CNS repair in human brains.

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