%0 Journal Article %J Science %D 2022 %T Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function %A Eraslan, Gökcen %A Drokhlyansky, Eugene %A Anand, Shankara %A Fiskin, Evgenij %A Subramanian, Ayshwarya %A Slyper, Michal %A Wang, Jiali %A Van Wittenberghe, Nicholas %A Rouhana, John M %A Waldman, Julia %A Ashenberg, Orr %A Lek, Monkol %A Dionne, Danielle %A Win, Thet Su %A Cuoco, Michael S %A Kuksenko, Olena %A Tsankov, Alexander M %A Branton, Philip A %A Marshall, Jamie L %A Greka, Anna %A Getz, Gad %A Segrè, Ayellet V %A Aguet, François %A Rozenblatt-Rosen, Orit %A Ardlie, Kristin G %A Regev, Aviv %K Biomarkers %K Cell Nucleus %K Disease %K Genome-Wide Association Study %K Humans %K Organ Specificity %K Phenotype %K RNA-Seq %X 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. %B Science %V 376 %P eabl4290 %8 2022 05 13 %G eng %N 6594 %1 http://www.ncbi.nlm.nih.gov/pubmed/35549429?dopt=Abstract %R 10.1126/science.abl4290