Multi-omic profiling of the developing human cerebral cortex at the single cell level

• DOI: 10.1101/2022.10.14.512250
• Publication Date: 2022-10-17T13:25:24Z
• Authors: 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
• Keywords: Cell type; Human brain; Gene regulatory network; Epigenomics

Abstract The cellular complexity of the human brain is established via dynamic changes in gene expression throughout development that mediated, part, by spatiotemporal activity cis-regulatory elements. We simultaneously profiled and chromatin accessibility 45,549 cortical nuclei across 6 broad developmental time-points from fetus to adult. identified cell-type specific domains which highly correlated with expression. Differentiation pseudotime trajectory analysis indicates at elements precedes transcription structure play a critical role neuronal lineage commitment. In addition, we mapped temporally genetic loci implicated neuropsychiatric traits, including schizophrenia bipolar disorder. Together, our results describe complex regulation cell composition stages determination, serve as blueprint shed light on impact alterations disease. One-Sentence Summary Simultaneous profiling single sheds fate determination cerebral cortex molecular basis