READING, WRITING, AND PERTURBING HUMAN NEURAL CELL BIOLOGY

Unraveling the complexity of human brain function demands integrated profiling, generation, and creative disruption of cell type-specific states to decode genotype-phenotype relationships. Here, I present a thesis tackling each of these areas. Profiling or “reading” of human brain tissue at the single cell level with technical innovations in transcriptomics provides deep molecular and cellular reference maps describing the landscape of human neural cell types. Generation or “writing” of synthetic human neural tissue using emerging human induced pluripotent stem cell differentiation technologies provides tractable cellular models to study human-specific neural cell biology. Disruption or “perturbing” of human neural tissue with pooled genome editing CRISPR screening systems enables scalable discovery of novel genotype-phenotype relationships. Continued work in these areas will enhance our understanding of how human neural phenotypes shift from healthy to diseased states and inform the development of new therapeutics and diagnostics to drive human neural phenotypes from diseased to healthy states.