UCSF

Microglia, the innate immune cells of the brain, are exquisitely sensitive to dynamic changes in the brain environment. They respond to extracellular signals in order to promote synapse formation and turnover, respond to tissue damage and pathogens, and clean up dead or dying cells. Ultimately, microglia are professional phagocytes; so how do they decide what to eat? This dissertation examines multiple transcriptomically and functionally distinct subpopulations of phagocytic microglia that shape the developing brain. Chapter 1 is an introduction to microglia with an emphasis on phagocytosis. Chapter 2 provides an introduction to single-cell sequencing of microglia through a mini-review of two papers published in 2019. Chapter 3 characterizes two populations of microglia in the developing zebrafish brain, showing that neuron-engulfing and synapse-associated microglia have distinct transcriptomic and morphological states depending on their local environment. Chapter 4 identifies a new molecular signature associated with microglia that are actively engulfing whole neurons in the developing murine brain. These transient interferon-responsive microglia restrict the accumulation of damaged neurons. Chapter 5 discusses the implications of this work and how carefully designing single cell sequencing experiments in combination with in situ work allows the functional and transcriptomic characterization of transient and rare populations.