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Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function.
Eraslan, Gökcen; Drokhlyansky, Eugene; Anand, Shankara; Fiskin, Evgenij; Subramanian, Ayshwarya; Slyper, Michal; Wang, Jiali; Van Wittenberghe, Nicholas; Rouhana, John M; Waldman, Julia; Ashenberg, Orr; Lek, Monkol; Dionne, Danielle; Win, Thet Su; Cuoco, Michael S; Kuksenko, Olena; Tsankov, Alexander M; Branton, Philip A; Marshall, Jamie L; Greka, Anna; Getz, Gad; Segrè, Ayellet V; Aguet, François; Rozenblatt-Rosen, Orit; Ardlie, Kristin G; Regev, Aviv.
Affiliation
  • Eraslan G; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Drokhlyansky E; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Anand S; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Fiskin E; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Subramanian A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Slyper M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wang J; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.
  • Van Wittenberghe N; Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.
  • Rouhana JM; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Waldman J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ashenberg O; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.
  • Lek M; Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.
  • Dionne D; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Win TS; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Cuoco MS; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kuksenko O; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
  • Tsankov AM; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Branton PA; Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Marshall JL; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Greka A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Getz G; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Segrè AV; The Joint Pathology Center Gynecologic/Breast Pathology, Silver Spring, MD 20910, USA.
  • Aguet F; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Rozenblatt-Rosen O; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ardlie KG; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Regev A; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Science ; 376(6594): eabl4290, 2022 05 13.
Article in En | MEDLINE | ID: mdl-35549429
ABSTRACT
Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Nucleus / Disease / RNA-Seq Limits: Humans Language: En Journal: Science Year: 2022 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Nucleus / Disease / RNA-Seq Limits: Humans Language: En Journal: Science Year: 2022 Type: Article Affiliation country: United States