Construction of a Multitissue Cell Atlas Reveals Cell‐Type‐Specific Regulation of Molecular and Complex Phenotypes in Pigs

Abstract The systematic characterization of cellular heterogeneity among tissues and cell‐type‐specific regulation underlying complex phenotypes remains elusive in pigs. Within the Pig Genotype‐Tissue Expression (PigGTEx) project, this work presents a single‐cell transcriptome atlas of adult pigs encompassing 229 268 high‐quality nuclei from 19 tissues, annotated to 67 major cell types. Besides cellular heterogeneity within and across tissues, this work further characterizes prominent tissue‐specific features and functions of muscle, epithelial, and immune cells. Through deconvoluting 3921 bulk RNA‐seq samples from 17 matching tissues, this work dissects thousands of genetic variants with cell‐type interaction effects on gene expression (ieQTL). By colocalizing these ieQTL with variants associated with 268 complex traits, new insights into the cellular mechanisms behind these traits are provided. Moreover, this work highlights that orthologous genes with cell‐type‐specific regulation in pigs exhibit significant heritability enrichment for some human complex phenotypes. Altogether, this work provides a valuable resource and highlights novel insights in cellular regulation of complex traits for accelerating pig precision breeding and human biomedical research.