Transcriptome and epigenome landscape of human cortical development modeled in organoids.

Published

Journal Article

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.

Full Text

Duke Authors

Cited Authors

  • Amiri, A; Coppola, G; Scuderi, S; Wu, F; Roychowdhury, T; Liu, F; Pochareddy, S; Shin, Y; Safi, A; Song, L; Zhu, Y; Sousa, AMM; PsychENCODE Consortium, ; Gerstein, M; Crawford, GE; Sestan, N; Abyzov, A; Vaccarino, FM

Published Date

  • December 2018

Published In

Volume / Issue

  • 362 / 6420

PubMed ID

  • 30545853

Pubmed Central ID

  • 30545853

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.aat6720

Language

  • eng