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A comparative atlas of single-cell chromatin accessibility in the human brain.
Li, Yang Eric; Preissl, Sebastian; Miller, Michael; Johnson, Nicholas D; Wang, Zihan; Jiao, Henry; Zhu, Chenxu; Wang, Zhaoning; Xie, Yang; Poirion, Olivier; Kern, Colin; Pinto-Duarte, Antonio; Tian, Wei; Siletti, Kimberly; Emerson, Nora; Osteen, Julia; Lucero, Jacinta; Lin, Lin; Yang, Qian; Zhu, Quan; Zemke, Nathan; Espinoza, Sarah; Yanny, Anna Marie; Nyhus, Julie; Dee, Nick; Casper, Tamara; Shapovalova, Nadiya; Hirschstein, Daniel; Hodge, Rebecca D; Linnarsson, Sten; Bakken, Trygve; Levi, Boaz; Keene, C Dirk; Shang, Jingbo; Lein, Ed; Wang, Allen; Behrens, M Margarita; Ecker, Joseph R; Ren, Bing.
  • Li YE; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Preissl S; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Miller M; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Johnson ND; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Wang Z; Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Jiao H; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Zhu C; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Wang Z; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Xie Y; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Poirion O; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Kern C; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Pinto-Duarte A; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Tian W; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Siletti K; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
  • Emerson N; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Osteen J; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Lucero J; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Lin L; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Yang Q; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Zhu Q; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Zemke N; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Espinoza S; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Yanny AM; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Nyhus J; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Dee N; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Casper T; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Shapovalova N; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Hirschstein D; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Hodge RD; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Linnarsson S; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
  • Bakken T; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Levi B; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Keene CD; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98104, USA.
  • Shang J; Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Lein E; Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • Wang A; Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
  • Behrens MM; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Ecker JR; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Ren B; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Science ; 382(6667): eadf7044, 2023 10 13.
Article en En | MEDLINE | ID: mdl-37824643
ABSTRACT
Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer's disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Atlas como Asunto / Encéfalo / Cromatina Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Atlas como Asunto / Encéfalo / Cromatina Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article