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DOI | 10.1126/science.aat6720 |
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.; Gerstein M.; Crawford G.E.; Sestan N.; Abyzov A.; Vaccarino F.M. | |
发表日期 | 2018 |
ISSN | 0036-8075 |
卷号 | 362期号:6420 |
英文摘要 | 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. © 2018 American Association for the Advancement of Science. All rights reserved. |
英文关键词 | transcriptome; transcriptome; biological development; brain; cell; disability; genetic analysis; genomics; molecular analysis; adult; Article; autism; brain cortex; brain development; clinical article; controlled study; down regulation; embryo; enhancer region; epigenetics; fetus; gene expression regulation; gene regulatory network; genetic analysis; genetic code; genetic variability; human; human cell; intellectual impairment; male; mental disease; organoid; pluripotent stem cell; priority journal; schizophrenia; biological model; cytology; embryology; gene expression regulation; genetic epigenesis; genetics; induced pluripotent stem cell; nervous system development; organoid; Cerebral Cortex; Enhancer Elements, Genetic; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; Induced Pluripotent Stem Cells; Models, Neurological; Neurogenesis; Organoids; Transcriptome |
语种 | 英语 |
来源期刊 | Science |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/242826 |
作者单位 | Child Study Center, Yale University, New Haven, CT 06520, United States; Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, United States; Department of Neuroscience, Yale University, New Haven, CT 06520, United States; National Research Foundation of Korea, Daejeon, South Korea; Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC 27708, United States; Department of Biostatistics, Yale School of Public Health, New Haven, CT, United States; Department of Molecular Biophysics and Biochemistry, Yale University, New haven, CT 06520, United States; Kavli Institute for Neuroscience, Yale University, New Haven, CT 06520, United States |
推荐引用方式 GB/T 7714 | Amiri A.,Coppola G.,Scuderi S.,et al. Transcriptome and epigenome landscape of human cortical development modeled in organoids[J],2018,362(6420). |
APA | Amiri A..,Coppola G..,Scuderi S..,Wu F..,Roychowdhury T..,...&Vaccarino F.M..(2018).Transcriptome and epigenome landscape of human cortical development modeled in organoids.Science,362(6420). |
MLA | Amiri A.,et al."Transcriptome and epigenome landscape of human cortical development modeled in organoids".Science 362.6420(2018). |
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