Single Cell Sequencing of TCF7L2 CRISPR Mutants Identifies Differentially Expressed Genes in Microglia
Morgan Haydock
Department of Biology
Faculty Supervisor: Nicholas Silva
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that consists of a range of social and communication impairments. Human postmortem patients with ASD have atypical brain development including altered synaptic density and microglia activation. Microglia are the resident immune cells in the brain with multiple functions during brain development and disease states including remodeling synapses and clearing apoptotic neurons. TCF7l2 is a high confidence risk gene in ASD. We have generated a TCF7L2 CRISPR mutant and performed single-cell mRNA sequencing on whole brain and microglia samples from the zebrafish. Our results have identified 25 transcriptionally unique clusters from both wild-type and TCF7L2 mutant brains. Annotation of cell types showed distinct tcf7l2 mutant and wild type microglia clusters. Importantly, differential gene expression (DEG) analysis revealed significant transcriptional differences in wild-type and TCF7L2 mutant microglia. These data reveal a prominent role for TCF7L2 in developing the transcriptome of microglia.