UCSF

My thesis investigates the role of brain-resident immune cells, particularly microglia, in angiogenesis during brain development and their impact on germinal matrix hemorrhage (GMH) in premature infants. While microglia were postulated to promote cerebrovascular formation, the exact mechanism remains unclear. To address this question, I developed a multidisciplinary approach to examine the distribution, transcriptomics, and functions of immune cell subtypes in distinct brain regions and ages. My findings showed that prenatal microglia age-dependently interact with nascent vasculature and that ablation of these cells reduces angiogenesis in the ganglionic eminences (GE), which correspond to the human germinal matrix. Furthermore, single-cell transcriptomics and flow cytometry showed that distinct subsets of immune cells employ diverse signaling mechanisms to promote vascular formation in the GE. In contrast, immune cells from preterm infants with GMH included neutrophils/monocytes that produce bactericidal factors and chemokine, which can disrupt vascular integrity and lead to GMH. Finally, my results showed that changes in microglia states adversely affect neural progenitor density and positioning. Taken together, this project offers insights into the complex tripartite interplay among immune, vascular, and neuronal cells during brain development, shedding light on their implications for GMH pathogenesis.