Single-cell genomics and regulatory networks for 388 human brains-Reference-Cited by-同舟云学术

Single-cell genomics and regulatory networks for 388 human brains

Published:2024-05-24 Issue:6698 Volume:384 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Emani Prashant S.¹²^ORCID,Liu Jason J.¹²^ORCID,Clarke Declan¹²^ORCID,Jensen Matthew¹²^ORCID,Warrell Jonathan¹²^ORCID,Gupta Chirag³⁴^ORCID,Meng Ran¹²^ORCID,Lee Che Yu⁵^ORCID,Xu Siwei⁵^ORCID,Dursun Cagatay¹²^ORCID,Lou Shaoke¹²,Chen Yuhang¹²^ORCID,Chu Zhiyuan¹^ORCID,Galeev Timur¹²^ORCID,Hwang Ahyeon⁵⁶^ORCID,Li Yunyang²⁷,Ni Pengyu¹²^ORCID,Zhou Xiao¹²^ORCID, ,Bakken Trygve E.⁸^ORCID,Bendl Jaroslav⁹¹⁰¹¹¹²^ORCID,Bicks Lucy¹³^ORCID,Chatterjee Tanima¹²^ORCID,Cheng Lijun¹⁴^ORCID,Cheng Yuyan¹³¹⁵,Dai Yi⁵,Duan Ziheng⁵^ORCID,Flaherty Mary¹⁴^ORCID,Fullard John F.⁹¹⁰¹¹¹²^ORCID,Gancz Michael¹²,Garrido-Martín Diego¹⁶^ORCID,Gaynor-Gillett Sophia¹⁴¹⁷^ORCID,Grundman Jennifer¹³^ORCID,Hawken Natalie¹³^ORCID,Henry Ella¹²,Hoffman Gabriel E.⁹¹⁰¹¹¹²¹⁸^ORCID,Huang Ao¹,Jiang Yunzhe¹²^ORCID,Jin Ting³⁴,Jorstad Nikolas L.⁸^ORCID,Kawaguchi Riki¹³¹⁹^ORCID,Khullar Saniya³⁴^ORCID,Liu Jianyin¹³,Liu Junhao⁵^ORCID,Liu Shuang⁴,Ma Shaojie²⁰²¹^ORCID,Margolis Michael^ORCID,Mazariegos Samantha¹³^ORCID,Moore Jill²²^ORCID,Moran Jennifer R.¹⁴^ORCID,Nguyen Eric¹²,Phalke Nishigandha²²^ORCID,Pjanic Milos⁹¹⁰¹¹¹²,Pratt Henry²²^ORCID,Quintero Diana¹³^ORCID,Rajagopalan Ananya S.⁷^ORCID,Riesenmy Tiernon R.²³^ORCID,Shedd Nicole²²^ORCID,Shi Manman¹⁴,Spector Megan¹⁴^ORCID,Terwilliger Rosemarie²⁴,Travaglini Kyle J.⁸^ORCID,Wamsley Brie¹³^ORCID,Wang Gaoyuan¹²^ORCID,Xia Yan¹²^ORCID,Xiao Shaohua¹³,Yang Andrew C.¹²,Zheng Suchen¹²^ORCID,Gandal Michael J.²⁵²⁶²⁷²⁸²⁹^ORCID,Lee Donghoon⁹¹⁰¹¹¹²^ORCID,Lein Ed S.⁸³⁰³¹^ORCID,Roussos Panos⁹¹⁰¹¹¹²¹⁸^ORCID,Sestan Nenad²⁰^ORCID,Weng Zhiping²²^ORCID,White Kevin P.³²^ORCID,Won Hyejung³³^ORCID,Girgenti Matthew J.²⁴³⁴³⁵^ORCID,Zhang Jing⁵^ORCID,Wang Daifeng³⁴³⁶^ORCID,Geschwind Daniel¹³¹⁹²⁶²⁷³⁷^ORCID,Gerstein Mark¹²⁷²³³⁸^ORCID,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,Cheng Lijun,Chess Andrew,Chien Jo-fan,Clement Ashley,Collado-Torres Leonardo,Cooper Gregory M.,Crawford Gregory E.,Dai Rujia,Daskalakis Nikolaos P.,Davila-Velderrain Jose,Deep-Soboslay Amy,Deng Chengyu,DiPietro Christopher P.,Dracheva Stella,Drusinsky Shiron,Duong Duc,Eagles Nicholas J.,Edelstein Jonathan,Galani Kiki,Girdhar Kiran,Goes Fernando S.,Greenleaf William,Guo Hanmin,Guo Qiuyu,Hadas Yoav,Hallmayer Joachim,Han Xikun,Haroutunian Vahram,He Chuan,Hicks Stephanie C.,Ho Marcus,Ho Li-Lun,Huang Yiling,Huuki-Myers Louise A.,Hyde Thomas M.,Iatrou Artemis,Inoue Fumitaka,Jajoo Aarti,Jiang Lihua,Jin Peng,Jops Connor,Jourdon Alexandre,Kellis Manolis,Kleinman Joel E.,Kleopoulos Steven P.,Kozlenkov Alex,Kriegstein Arnold,Kundaje Anshul,Kundu Soumya,Li Junhao,Li Mingfeng,Lin Xiao,Liu Shuang,Liu Chunyu,Loupe Jacob M.,Lu Dan,Ma Liang,Mariani Jessica,Martinowich Keri,Maynard Kristen R.,Myers Richard M.,Micallef Courtney,Mikhailova Tatiana,Ming Guo-li,Mohammadi Shahin,Monte Emma,Montgomery Kelsey S.,Mukamel Eran A.,Nairn Angus C.,Nemeroff Charles B.,Norton Scott,Nowakowski Tomasz,Omberg Larsson,Page Stephanie C.,Park Saejeong,Patowary Ashok,Pattni Reenal,Pertea Geo,Peters Mette A.,Pinto Dalila,Pochareddy Sirisha,Pollard Katherine S.,Pollen Alex,Przytycki Pawel F.,Purmann Carolin,Qin Zhaohui S.,Qu Ping-Ping,Raj Towfique,Reach Sarah,Reimonn Thomas,Ressler Kerry J.,Ross Deanna,Rozowsky Joel,Ruth Misir,Ruzicka W. Brad,Sanders Stephan J.,Schneider Juliane M.,Scuderi Soraya,Sebra Robert,Seyfried Nicholas,Shao Zhiping,Shieh Annie W.,Shin Joo Heon,Skarica Mario,Snijders Clara,Song Hongjun,State Matthew W.,Stein Jason,Steyert Marilyn,Subburaju Sivan,Sudhof Thomas,Snyder Michael,Tao Ran,Therrien Karen,Tsai Li-Huei,Urban Alexander E.,Vaccarino Flora M.,van Bakel Harm,Vo Daniel,Voloudakis Georgios,Wang Tao,Wang Sidney H.,Wang Yifan,Wei Yu,Weimer Annika K.,Weinberger Daniel R.,Wen Cindy,Whalen Sean,Willsey A. Jeremy,Wong Wing,Wu Hao,Wu Feinan,Wuchty Stefan,Wylie Dennis,Yap Chloe X.,Zeng Biao,Zhang Pan,Zhang Chunling,Zhang Bin,Zhang Yanqiong,Ziffra Ryan,Zeier Zane R.,Zintel Trisha M.

Affiliation:

1. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.

2. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.

3. Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USA.

4. Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.

5. Department of Computer Science, University of California, Irvine, CA 92697, USA.

6. Mathematical, Computational and Systems Biology, University of California, Irvine, CA 92697, USA.

7. Department of Computer Science, Yale University, New Haven, CT 06520, USA.

8. Allen Institute for Brain Science, Seattle, WA 98109, USA.

9. Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

10. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

11. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

12. Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

13. Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

14. Tempus Labs, Chicago, IL 60654, USA.

15. Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

16. Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Barcelona 08028, Spain.

17. Department of Biology, Cornell College, Mount Vernon, IA 52314, USA.

18. Mental Illness Research Education and Clinical Center, James J. Peters VA Medical Center, Bronx, NY 10468, USA.

19. Center for Autism Research and Treatment, Semel Institute, University of California, Los Angeles, CA 90095, USA.

20. Department of Neuroscience, Yale University, New Haven, CT 06510, USA.

21. Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

22. Department of Genomics and Computational Biology, UMass Chan Medical School, Worcester, MA 01605, USA.

23. Department of Statistics and Data Science, Yale University, New Haven, CT 06520, USA.

24. Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA.

25. Interdepartmental Program in Bioinformatics, University of California, Los Angeles, Los Angeles CA, 90095, USA.

26. Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

27. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

28. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

29. Lifespan Brain Institute, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

30. Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA.

31. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.

32. Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore.

33. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

34. Wu Tsai Institute, Yale University, New Haven, CT 06520, USA.

35. Clinical Neuroscience Division, National Center for Posttraumatic Stress Disorder, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA.

36. Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.

37. Institute for Precision Health, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

38. Department of Biomedical Informatics & Data Science, Yale University, New Haven, CT 06520, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adi5199

Reference248 articles.

1. Defining the Genetic, Genomic, Cellular, and Diagnostic Architectures of Psychiatric Disorders

2. Revealing the brain's molecular architecture

3. The road to precision psychiatry: translating genetics into disease mechanisms

4. Comprehensive functional genomic resource and integrative model for the human brain

5. The GTEx Consortium atlas of genetic regulatory effects across human tissues

Cited by 6 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Comparative single‐cell transcriptomic analysis across tissues of aging primates reveals specific autologous activation of ZNF281 to mitigate oxidative stress in cornea;Aging Cell;2024-09-10

2. Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids;2024-09-03

3. Organizational principles of the primate cerebral cortex at the single-cell level;2024-07-07

4. Remedy hope for polycystic ovary syndrome;Science;2024-06-14

5. Single Cell Transcriptome Defines Cell Type Repertoire of AdultDaphnia magna;2024-05-30