Talk Title: Dissecting Human Brain Development and Neuropsychiatric Disorders with Single-Cell and Spatial 3D-Multiomics
Abstract: Our research program develops single-cell and spatial technologies to study the genetic and epigenomic basis of human diseases. Human brain development is guided by gene regulatory programs that define neurogenic regions and give rise to diverse brain structures. Excitatory neurons arise from the ventricular zone (VZ), while inhibitory interneurons and striatal medium spiny neurons (MSNs) originate from the ganglionic eminences (GEs). The molecular programs that regionalize GE subtypes (MGE, LGE, CGE) and cortical areas (e.g., frontal vs. temporal) remain poorly understood. We used single-nucleus methyl-3C sequencing (snm3C-seq) and highly multiplexed spatial transcriptomics to profile DNA methylation and 3D genome architecture across GEs, striatum, hippocampus, and cortical regions spanning prenatal to adult stages. We reconstructed developmental trajectories and identified region- and stage-specific regulatory programs. In our effort to identify the single cell DNA methylation signatures of autism spectrum disorder (ASD), we profiled >60,000 nuclei using snmCT-seq across 26 ASD and 23 neurotypical donors and identified thousands of differentially methylated regions (DMRs), enriched in promoters and cell-type-specific regulatory elements. ASD-associated methylation signatures are moderate compared to age-related changes and were largely uncorrelated with gene expression. The age-related changes in CG and non-CG sequence contexts and age-by-ASD interactions highlight areas of future research interests.
Date: Tuesday, April 14th 2026
Time: 10:00 AM
Note: Virtual attendance option is available upon special request. Email CNCM@uci.edu for all requests.
