| Title: |
Single-cell genomics and regulatory networks for 388 human brains |
| Authors: |
Emani, Prashant S; Liu, Jason J; Clarke, Declan; Jensen, Matthew; Warrell, Jonathan; Gupta, Chirag; Meng, Ran; Lee, Che Yu; Xu, Siwei; Dursun, Cagatay; Lou, Shaoke; Chen, Yuhang; Chu, Zhiyuan; Galeev, Timur; Hwang, Ahyeon; Li, Yunyang; Ni, Pengyu; Zhou, Xiao; Bakken, Trygve E; Bendl, Jaroslav; Bicks, Lucy; Chatterjee, Tanima; Cheng, Lijun; Cheng, Yuyan; Dai, Yi; Duan, Ziheng; Flaherty, Mary; Fullard, John F; Gancz, Michael; Garrido-Martín, Diego; Gaynor-Gillett, Sophia; Grundman, Jennifer; Hawken, Natalie; Henry, Ella; Hoffman, Gabriel E; Huang, Ao; Jiang, Yunzhe; Jin, Ting; Jorstad, Nikolas L; Kawaguchi, Riki; Khullar, Saniya; Liu, Jianyin; Liu, Junhao; Liu, Shuang; Ma, Shaojie; Margolis, Michael; Mazariegos, Samantha; Moore, Jill; Moran, Jennifer R; Nguyen, Eric; Phalke, Nishigandha; Pjanic, Milos; Pratt, Henry; Quintero, Diana; Rajagopalan, Ananya S; Riesenmy, Tiernon R; Shedd, Nicole; Shi, Manman; Spector, Megan; Terwilliger, Rosemarie; Travaglini, Kyle J; Wamsley, Brie; Wang, Gaoyuan; Xia, Yan; Xiao, Shaohua; Yang, Andrew C; Zheng, Suchen; Gandal, Michael J; Lee, Donghoon; Lein, Ed S; Roussos, Panos; Sestan, Nenad; Weng, Zhiping; White, Kevin P; Won, Hyejung; Girgenti, Matthew J; Zhang, Jing; Wang, Daifeng; Geschwind, Daniel; Gerstein, Mark; Akbarian, Schahram; Abyzov, Alexej; Ahituv, Nadav; Arasappan, Dhivya; Almagro Armenteros, Jose Juan; Beliveau, Brian J; Berretta, Sabina; Bharadwaj, Rahul A; Bhattacharya, Arjun; Brennand, Kristen; Capauto, Davide; Champagne, Frances A; Chatzinakos, Chris; Chen, H Isaac; Chess, Andrew; Chien, Jo-fan; Clement, Ashley; Collado-Torres, Leonardo; Cooper, Gregory M |
| Source: |
Science, vol 384, iss 6698 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2024 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
3101 Biochemistry and Cell Biology (for-2020); 3105 Genetics (for-2020); 31 Biological Sciences (for-2020); Neurosciences (rcdc); Genetics (rcdc); Brain Disorders (rcdc); Mental Health (rcdc); Biotechnology (rcdc); Human Genome (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); 1.1 Normal biological development and functioning (hrcs-rac); Humans (mesh); Aging (mesh); Brain (mesh); Cell Communication (mesh); Chromatin (mesh); Gene Regulatory Networks (mesh); Genomics (mesh); Mental Disorders (mesh); Prefrontal Cortex (mesh); Quantitative Trait Loci (mesh); Single-Cell Analysis (mesh); PsychENCODE Consortium‡; PsychENCODE Consortium; General Science & Technology (science-metrix) |
| Time: |
eadi5199 |
| Description: |
Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt3cs7f3r3; https://escholarship.org/uc/item/3cs7f3r3; https://escholarship.org/content/qt3cs7f3r3/qt3cs7f3r3.pdf |
| DOI: |
10.1126/science.adi5199 |
| Availability: |
https://escholarship.org/uc/item/3cs7f3r3; https://escholarship.org/content/qt3cs7f3r3/qt3cs7f3r3.pdf; https://doi.org/10.1126/science.adi5199 |
| Rights: |
public |
| Accession Number: |
edsbas.97E4F688 |
| Database: |
BASE |