TY - JOUR
T1 - Transcriptome and epigenome landscape of human cortical development modeled in organoids
AU - Amiri, Anahita
AU - Coppola, Gianfilippo
AU - Scuderi, Soraya
AU - Wu, Feinan
AU - Roychowdhury, Tanmoy
AU - Liu, Fuchen
AU - Pochareddy, Sirisha
AU - Shin, Yurae
AU - Safi, Alexias
AU - Song, Lingyun
AU - Zhu, Ying
AU - Sousa, André M.M.
AU - Gerstein, Mark
AU - Crawford, Gregory E.
AU - Sestan, Nenad
AU - Abyzov, Alexej
AU - Vaccarino, Flora M.
N1 - Publisher Copyright:
© 2018 American Association for the Advancement of Science. All rights reserved.
PY - 2018/12/14
Y1 - 2018/12/14
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aat6720
DO - 10.1126/science.aat6720
M3 - Article
C2 - 30545853
AN - SCOPUS:85058398161
SN - 0036-8075
VL - 362
JO - Science
JF - Science
IS - 6420
M1 - 1268
ER -