Massively parallel characterization of regulatory elements in the developing human cortex Article Swipe

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Chengyu Deng , Sean Whalen , Marilyn Steyert , Ryan Ziffra , Pawel F. Przytycki , Fumitaka Inoue , Daniela A. Pereira , Davide Capauto , Scott Norton , Flora M. Vaccarino , Alex A. Pollen , Tomasz J. Nowakowski , Nadav Ahituv , Katherine S. Pollard , Schahram Akbarian , Alexej Abyzov , Nadav Ahituv , Dhivya Arasappan , José Juan Almagro Armenteros , Brian J. Beliveau , Jaroslav Bendl , Sabina Berretta , Rahul Bharadwaj , Arjun Bhattacharya , Lucy Bicks , Kristen Brennand , Davide Capauto , Frances A. Champagne , Tanima Chatterjee , Chris Chatzinakos , Yuhang Chen , H. Isaac Chen , Yuyan Cheng , Lijun Cheng , Andrew Chess , Jo-fan Chien , Zhiyuan Chu , Declan Clarke , Ashley Clement , Leonardo Collado‐Torres , Gregory M. Cooper , Gregory E. Crawford , Rujia Dai , Nikolaos P. Daskalakis , José Dávila-Velderrain , Amy Deep‐Soboslay , Chengyu Deng , Christopher P. DiPietro , Stella Dracheva , Shiron Drusinsky , Ziheng Duan , Duc M. Duong , Cagatay Dursun , Nicholas J. Eagles , Jonathan I. Edelstein , Prashant S. Emani , John F. Fullard , Kiki Galani , Timur R. Galeev , Michael J. Gandal , Sophia C. Gaynor , Mark Gerstein , Daniel H. Geschwind , Kiran Girdhar , Fernando S. Goes , William J. Greenleaf , Jennifer Grundman , Hanmin Guo , Qiuyu Guo , Chirag Gupta , Yoav Hadas , Joachim Hallmayer , Xikun Han , Vahram Haroutunian , Natalie Hawken , Chuan He , Ella Henry , Stephanie C. Hicks , Marcus Ho , Li‐Lun Ho , Gabriel E. Hoffman , Yi‐Ling Huang , Louise A. Huuki-Myers , Ahyeon Hwang , Thomas M. Hyde , Artemis Iatrou , Fumitaka Inoue , Aarti Jajoo , Matthew L. Jensen , Lihua Jiang , Jin Peng , Ting Jin , Connor Jops , Alexandre Jourdon , Riki Kawaguchi , Manolis Kellis , Saniya Khullar , Joel E. Kleinman , Steven P. Kleopoulos , Alexey Kozlenkov ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1126/science.adh0559

Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type–specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.

Related Topics

Biology

Chromatin

Organoid

Computational Biology

Concepts

Enhancer Biology Regulatory sequence Chromatin Organoid Computational biology Gene Reporter gene Regulation of gene expression Massively parallel Corticogenesis Cell biology Neuroscience Transcription factor Gene expression Genetics Embryonic stem cell Computer science Parallel computing

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Type: article
Language: en
Landing Page: https://doi.org/10.1126/science.adh0559
OA Status: gold
Cited By: 46
References: 97
Related Works: 10
OpenAlex ID: https://openalex.org/W4398250017

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OpenAlex ID: https://openalex.org/W4398250017

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DOI: https://doi.org/10.1126/science.adh0559

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Title: Massively parallel characterization of regulatory elements in the developing human cortex

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Type: article

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Language: en

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Publication year: 2024

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Publication date: 2024-05-23

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Authors: Chengyu Deng, Sean Whalen, Marilyn Steyert, Ryan Ziffra, Pawel F. Przytycki, Fumitaka Inoue, Daniela A. Pereira, Davide Capauto, Scott Norton, Flora M. Vaccarino, Alex A. Pollen, Tomasz J. Nowakowski, Nadav Ahituv, Katherine S. Pollard, Schahram Akbarian, Alexej Abyzov, Nadav Ahituv, Dhivya Arasappan, José Juan Almagro Armenteros, Brian J. Beliveau, Jaroslav Bendl, Sabina Berretta, Rahul Bharadwaj, Arjun Bhattacharya, Lucy Bicks, Kristen Brennand, Davide Capauto, Frances A. Champagne, Tanima Chatterjee, Chris Chatzinakos, Yuhang Chen, H. Isaac Chen, Yuyan Cheng, Lijun Cheng, Andrew Chess, Jo-fan Chien, Zhiyuan Chu, Declan Clarke, Ashley Clement, Leonardo Collado‐Torres, Gregory M. Cooper, Gregory E. Crawford, Rujia Dai, Nikolaos P. Daskalakis, José Dávila-Velderrain, Amy Deep‐Soboslay, Chengyu Deng, Christopher P. DiPietro, Stella Dracheva, Shiron Drusinsky, Ziheng Duan, Duc M. Duong, Cagatay Dursun, Nicholas J. Eagles, Jonathan I. Edelstein, Prashant S. Emani, John F. Fullard, Kiki Galani, Timur R. Galeev, Michael J. Gandal, Sophia C. Gaynor, Mark Gerstein, Daniel H. Geschwind, Kiran Girdhar, Fernando S. Goes, William J. Greenleaf, Jennifer Grundman, Hanmin Guo, Qiuyu Guo, Chirag Gupta, Yoav Hadas, Joachim Hallmayer, Xikun Han, Vahram Haroutunian, Natalie Hawken, Chuan He, Ella Henry, Stephanie C. Hicks, Marcus Ho, Li‐Lun Ho, Gabriel E. Hoffman, Yi‐Ling Huang, Louise A. Huuki-Myers, Ahyeon Hwang, Thomas M. Hyde, Artemis Iatrou, Fumitaka Inoue, Aarti Jajoo, Matthew L. Jensen, Lihua Jiang, Jin Peng, Ting Jin, Connor Jops, Alexandre Jourdon, Riki Kawaguchi, Manolis Kellis, Saniya Khullar, Joel E. Kleinman, Steven P. Kleopoulos, Alexey Kozlenkov

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Landing page: https://doi.org/10.1126/science.adh0559

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OA status: gold

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Concepts: Enhancer, Biology, Regulatory sequence, Chromatin, Organoid, Computational biology, Gene, Reporter gene, Regulation of gene expression, Massively parallel, Corticogenesis, Cell biology, Neuroscience, Transcription factor, Gene expression, Genetics, Embryonic stem cell, Computer science, Parallel computing

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Cited by: 46

Total citation count in OpenAlex
Citations by year (recent): 2025: 29, 2024: 16, 2023: 1

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References (count): 97

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Related works (count): 10

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