Construction of a multi-tissue cell atlas reveals cell-type-specific regulation of molecular and complex phenotypes in pigs

Lijuan Chen; Houcheng Li; Jinyan Teng; Zhen Wang; Xiaolu Qu; Zhe Chen; Xiaodian Cai; Haonan Zeng; Zhonghao Bai; Jinghui Li; Xiangchun Pan; Leyan Yan; Fei Wang; Lin Lin; Yonglun Luo; Goutam Sahana; Mogens Sandø Lund; María Ballester; Daniel Crespo‐Piazuelo; Peter Karlskov‐Mortensen; Merete Fredholm; Alex Clop; Marcel Amills; Crystal Lynn Loving; Christopher Keith Tuggle; Ole Madsen; Jiaqi Li; Zhe Zhang; George E. Liu; Jicai Jiang

doi:10.1002/advs.202504961

GeneticsAdvanced ScienceNov 27, 2025

Peer-reviewed journal article

Construction of a multi-tissue cell atlas reveals cell-type-specific regulation of molecular and complex phenotypes in pigs

Lijuan Chen iD, Houcheng Li iD, Jinyan Teng iD, Zhen Wang iD, Xiaolu Qu iD, Zhe Chen iD, Xiaodian Cai iD, Haonan Zeng iD, Zhonghao Bai iD, Jinghui Li iD, Xiangchun Pan iD, Leyan Yan iD, Fei Wang iD, Lin Lin iD, Yonglun Luo iD, Goutam Sahana iD, Mogens Sandø Lund iD, María Ballester iD, Daniel Crespo‐Piazuelo iD, Peter Karlskov‐Mortensen iD, Merete Fredholm iD, Alex Clop iD, Marcel Amills iD, Crystal Lynn Loving iD, Christopher Keith Tuggle iD, , Guoqiang Yi iD

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, we present 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, we further characterize prominent tissue-specific features and functions of muscle, epithelial, and immune cells. Through deconvoluting 3,921 bulk RNA-seq samples from 17 matching tissues, we dissect thousands of genetic variants with cell-type interaction effects on gene expression (ieQTL). By colocalizing these ieQTL with variants associated with 268 complex traits, we provide new insights into the cellular mechanisms behind these traits. Moreover, we highlight that orthologous genes with cell-type-specific regulation in pigs exhibit significant heritability enrichment for some human complex phenotypes. Altogether, our work provides a valuable resource and highlights novel insights in cellular regulation of complex traits for accelerating pig precision breeding and human biomedical research.

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