Multi-omic profiling of the developing human cerebral cortex at the single cell level
Kaiyi Zhu, Jaroslav Bendl, Samir Rahman, James M. Vicari, Claire Coleman, Tereza Clarence, Ovaun Latouche, Nadejda M. Tsankova, Aiqun Li, Kristen J. Brennand, Donghoon Lee, Guo-Cheng Yuan, John F. Fullard, Panos Roussos
Abstract
The cellular complexity of the human brain is established via dynamic changes in gene expression throughout development that is mediated, in part, by the spatiotemporal activity of cis-regulatory elements (CREs). We simultaneously profiled gene expression and chromatin accessibility in 45,549 cortical nuclei across six broad developmental time points from fetus to adult. We identified cell type–specific domains in which chromatin accessibility is highly correlated with gene expression. Differentiation pseudotime trajectory analysis indicates that chromatin accessibility at CREs precedes transcription and that dynamic changes in chromatin structure play a critical role in neuronal lineage commitment. In addition, we mapped cell type–specific and temporally specific genetic loci implicated in neuropsychiatric traits, including schizophrenia and bipolar disorder. Together, our results describe the complex regulation of cell composition at critical stages in lineage determination and shed light on the impact of spatiotemporal alterations in gene expression on neuropsychiatric disease.
Datasets
1. 10x scRNA-seq from human cortex
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Source data
https://cellxgene.cziscience.com/collections/ceb895f4-ff9f-403a-b7c3-187a9657ac2c
Alias names
GSE204684, SCP1859, PMID37824614, PMC10569714
Cite this study
Zhu, K., Bendl, J., Rahman, S., Vicari, J.M., Coleman, C., Clarence, T., Latouche, O., Tsankova, N.M., Li, A., Brennand, K.J. and Lee, D., 2023. Multi-omic profiling of the developing human cerebral cortex at the single-cell level. Science Advances, 9(41), p.eadg3754. https://doi.org/10.1126/sciadv.adg3754