In bioRxiv : the preprint server for biology
UNLABELLED : Nucleotide changes in gene regulatory elements are important determinants of neuronal development and disease. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis -regulatory activity of 102,767 sequences, including differentially accessible cell-type specific regions in the developing cortex and single-nucleotide variants associated with psychiatric disorders. In primary cells, we identified 46,802 active enhancer sequences and 164 disorder-associated variants that significantly alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning, we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.
ONE SENTENCE SUMMARY : We identify 46,802 enhancers and 164 psychiatric disorder variants with regulatory effects in the developing cortex and organoids.
Deng Chengyu, Whalen Sean, Steyert Marilyn, Ziffra Ryan, Przytycki Pawel F, Inoue Fumitaka, Pereira Daniela A, Capauto Davide, Norton Scott, Vaccarino Flora M, Pollen Alex, Nowakowski Tomasz J, Ahituv Nadav, Pollard Katherine S
2023-Feb-16
