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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
Science (American Association for the Advancement of Science), 05/2022, Volume: 376, Issue: 6594Journal Article
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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