Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk.
Publication/Presentation Date
12-14-2018
Abstract
To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type-specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Developmentally regulated chromosomal conformation changes at schizophrenia-relevant sequences disproportionally occurred in neurons, highlighting the existence of cell type-specific disease risk vulnerabilities in spatial genome organization.
Volume
362
Issue
6420
ISSN
1095-9203
Published In/Presented At
Rajarajan, P., Borrman, T., Liao, W., Schrode, N., Flaherty, E., Casiño, C., Powell, S., Yashaswini, C., LaMarca, E. A., Kassim, B., Javidfar, B., Espeso-Gil, S., Li, A., Won, H., Geschwind, D. H., Ho, S. M., MacDonald, M., Hoffman, G. E., Roussos, P., Zhang, B., … Akbarian, S. (2018). Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk. Science (New York, N.Y.), 362(6420), eaat4311. https://doi.org/10.1126/science.aat4311
Disciplines
Medicine and Health Sciences
PubMedID
30545851
Department(s)
Medical Education
Document Type
Article