How do genes contribute to development and disease?
Gene expression networks provide the underlying template for nervous system development. These fine-tuned, evolutionarily conserved networks have remarkable cell-type and developmental stage-specificity. For the first time, investigators in DNB have the tools to blueprint gene expression networks on a genome-wide scale with single cell resolution. How is this remarkable specificity achieved? How do gene expression networks contribute to evolutionary adaptation? Are gene networks disrupted in predictable ways during disease progression? Can we exploit these networks to develop novel therapies for cancer, degeneration and other neurologic diseases? Together, experimentalists work with data scientists to provide unprecedented new insights into genome function and structure to serve our mission.
The realization that medulloblastoma consists of distinct molecular subgroups has motivated basic scientists to investigate the biological origins of the disease. To identify the cellular origins of these subgroups, Dr. Northcott’s team used single-cell RNA sequencing to analyze 25 tumors from patients with medulloblastoma. The team uncovered unique cellular programs within each subgroup. The discovery is expected to accelerate the development of improved methods for classifying these tumors, expand our understanding of the clinical significance of intermediate Group 3/Group 4 tumors, and provide insight into their treatment.
The Polycomb repressive complex 2 (PRC2) is a crucial chromatin modifier in executing neurodevelopmental programs. Work from the Peng lab finds that PRC2 interacts with the nucleic acid-binding protein Ybx1. These findings suggest that Ybx1 fine-tunes PRC2 activities to regulate spatiotemporal gene expression in embryonic neural development and uncover a crucial epigenetic mechanism balancing forebrain-hindbrain lineages and self-renewal-differentiation choices in NPCs.