Transcriptome and epigenome landscape of human cortical development modeled in organoids. 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., PsychENCODE Consortium, Gerstein, M., Crawford, G. E., Sestan, N., Abyzov, A., & Vaccarino, F. M. Science (New York, N.Y.), 2018. 00010 doi abstract bibtex 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.
@article{amiri_transcriptome_2018,
title = {Transcriptome and epigenome landscape of human cortical development modeled in organoids},
volume = {362},
issn = {1095-9203},
doi = {10.1126/science.aat6720},
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.},
language = {eng},
number = {6420},
journal = {Science (New York, N.Y.)},
author = {Amiri, Anahita and Coppola, Gianfilippo and Scuderi, Soraya and Wu, Feinan and Roychowdhury, Tanmoy and Liu, Fuchen and Pochareddy, Sirisha and Shin, Yurae and Safi, Alexias and Song, Lingyun and Zhu, Ying and Sousa, André M. M. and {PsychENCODE Consortium} and Gerstein, Mark and Crawford, Gregory E. and Sestan, Nenad and Abyzov, Alexej and Vaccarino, Flora M.},
year = {2018},
pmid = {30545853},
pmcid = {PMC6426303},
note = {00010 },
keywords = {Cerebral Cortex, Enhancer Elements, Genetic, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Humans, Induced Pluripotent Stem Cells, Models, Neurological, Neurogenesis, Organoids, Transcriptome}
}
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