Transcriptome and epigenome landscape of human cortical development modeled in organoids

Anahita Amiri, Gianfilippo Coppola, Soraya Scuderi, Feinan Wu, Tanmoy Roychowdhury, Fuchen Liu, Sirisha Pochareddy, Yurae Shin, Alexias Safi, Lingyun Song, Ying Zhu, André M.M. Sousa, Mark Gerstein, Gregory E. Crawford, Nenad Sestan, Alexej Abyzov, Flora M. Vaccarino

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1268
JournalScience
Volume362
Issue number6420
DOIs
StatePublished - Dec 14 2018

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Amiri, A., Coppola, G., Scuderi, S., Wu, F., Roychowdhury, T., Liu, F., Pochareddy, S., Shin, Y., Safi, A., Song, L., Zhu, Y., Sousa, A. M. M., Gerstein, M., Crawford, G. E., Sestan, N., Abyzov, A., & Vaccarino, F. M. (2018). Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science, 362(6420), [1268]. https://doi.org/10.1126/science.aat6720