We’re bringing together leaders in cancer research.
Speaker
Chongyuan Luo, PhD
Assistant Professor
Human Genetics
University of California, Los Angeles
“Dissecting Human Brain Development and Prostate Cancer Evolution with Single-Cell and Spatial 3D-Multiomics”
Our research program develops single-cell and spatial technologies to study the genomic 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. Inhibitory interneurons and striatal medium spiny neurons (MSNs) originate from the ganglionic eminences (GEs), whereas excitatory neurons arise from the ventricular zone (VZ). The molecular programs that regionalize GE subtypes (MGE, LGE, CGE) and cortical areas remain poorly understood. We used single-nucleus methyl-3C sequencing (snm3C-seq), highly multiplex spatial transcriptomics, and chromatin+RNA MERFISH to investigate the 3D multi-omic architecture across GEs, the striatum, the hippocampus, and cortical regions spanning prenatal to adult stages. The study uncovers distinct 3D multi-omic programs in the three GE regions during brain development: MGEand CGE-derived interneurons show continuous subtypes and temporally separated trajectories of the DNA methylome and 3D genome, whereas LGE-derived MSNs display highly discrete subtypes with temporally synchronized multi-modal dynamics.
The ever-evolving cancer genome provides an exceptional opportunity to investigate the interaction between intratumoral genetic and epigenetic heterogeneity. We have developed computational approaches that integrate snm3C-seq and population-scale bulk profiles to determine the epigenomic and genomic subtypes of true single tumor cells. Using such unique experimental and computational strategies, we are investigating intra-tumoral, spatial, and subclonal methylome-genome evolution in prostate tumors.