Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function-Reference-Cited by-同舟云学术

Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

Published:2022-05-13 Issue:6594 Volume:376 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Eraslan Gökcen¹^ORCID,Drokhlyansky Eugene¹^ORCID,Anand Shankara²^ORCID,Fiskin Evgenij¹^ORCID,Subramanian Ayshwarya¹^ORCID,Slyper Michal¹^ORCID,Wang Jiali³⁴⁵^ORCID,Van Wittenberghe Nicholas¹^ORCID,Rouhana John M.³⁴⁵,Waldman Julia¹^ORCID,Ashenberg Orr¹^ORCID,Lek Monkol⁶,Dionne Danielle¹^ORCID,Win Thet Su⁷,Cuoco Michael S.¹^ORCID,Kuksenko Olena¹^ORCID,Tsankov Alexander M.⁸^ORCID,Branton Philip A.⁹^ORCID,Marshall Jamie L.²^ORCID,Greka Anna²¹⁰^ORCID,Getz Gad²¹¹¹²^ORCID,Segrè Ayellet V.³⁴⁵^ORCID,Aguet François²^ORCID,Rozenblatt-Rosen Orit¹^ORCID,Ardlie Kristin G.²^ORCID,Regev Aviv¹¹³^ORCID

Affiliation:

1. Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

2. The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

3. Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.

4. Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.

5. Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

6. Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.

7. Department of Dermatology, Brigham and Women’s Hospital, Boston, MA 02115, USA.

8. Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

9. The Joint Pathology Center Gynecologic/Breast Pathology, Silver Spring, MD 20910, USA.

10. Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.

11. Center for Cancer Research and Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.

12. Harvard Medical School, Boston, MA 02115, USA.

13. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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