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 e...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.展开更多
文摘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.
