Transcriptome and epigenome landscape of human cortical development modeled in organoids

• DOI: 10.1126/science.aat6720
• Publication Date: 2018-12-14T00:05:16Z
• Authors: 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; Schahram Akbarian; Joon-Yong An; Christoper Armoskus; Allison E. Ashley...; Thomas G. Beach; Judson Belmont; Jaroslav Bendl; Tyler Borrman; Leanne Brown; Miguel Brown; Mimi Brown; Tonya Brunetti; Julien Bryois; Emily E. Burke; Adrian Camarena; Becky C. Carlyle; Yooree Chae; Alexander W. Charney; Chao Chen; Lijun Cheng; Adriana Cherskov; Jinmyung Choi; Declan Clarke; Leonardo Collado-...; Rujia Dai; Luis De La Torre ...; Diane DelValle; Olivia Devillers; Stella Dracheva; Prashant S. Emani; Oleg V. Evgrafov; Peggy J. Farnham; Dominic Fitzgerald; Elie Flatow; Nancy Francoeur; John F. Fullard; Michael J. Gandal; Tianliuyun Gao; Melanie E. Garrett; Daniel H. Geschwind; Gina Giase; Kiran Girdhar; Paola Giusti-Rodr...; Fernando S. Goes; Thomas Goodman; Kay S. Grennan; Mengting Gu; Gamze Gürsoy; Evi Hadjimichael; Chang-Gyu Hahn; Vahram Haroutunian; Mads E. Hauberg; Gabriel E. Hoffman; Jack Huey; Thomas M. Hyde; Nikolay A. Ivanov; Rivka Jacobov; Andrew E. Jaffe; Yan Jiang; Yi Jiang; Graham D. Johnson; Bibi S. Kassim; Amira Kefi; Yunjung Kim; Robert R. Kitchen; Joel E. Kleiman; James A. Knowles; Alexey Kozlenkov; Mingfeng Li; Zhen Li; Barbara K. Lipska; Chunyu Liu; Shuang Liu; Lara M. Mangravite; Jessica Mariani; Eugenio Mattei; Daniel J. Miller; Jill Moore; Angus C. Nairn; Fabio C. P. Navarro; Royce B. Park; Mette A. Peters; Dalila Pinto; Sirisha Pochareddy; Damon Polioudakis; Henry Pratt; Amanda J. Price; Michael Purcaro; Mohana Ray; Timothy E. Reddy; Suhn K. Rhie; Panos Roussos; Stephan J. Sanders; Gabriel Santpere; Shannon Schreiner; Brooke Sheppard; Xu Shi; Annie W. Shieh; Joo Heon Shin; Mario Skarica; Lingyun Song; Andre M.M. Sousa; Valeria N. Spitsyna; Matthew W. State; Patrick F. Sullivan; Vivek Swarup; Jin Szatkiewicz; Anna Szekely; Ran Tao; Harm van Bakel; Yongjun Wang; Daifeng Wang; Jonathan Warrell; Maree J. Webster; Sherman Weissman; Zhiping Weng; Donna M. Werling; Kevin P. White; Jeremy A. Willsey; Jennifer R. Wiseman; Heather Witt; Hyejung Won; Gregory A. Wray; Yan Xia; Min Xu; Yucheng T. Yang; Mo Yang; Peter Zandi; Jing Zhang; Elizabeth Zharovsky
• Keywords: Epigenome; Organoid; Human brain; Gene regulatory network

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