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Research Project: Accelerating Genetic Improvement of Ruminants Through Enhanced Genome Assembly, Annotation, and Selection

Location: Animal Genomics and Improvement Laboratory

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

Author
item CHEN, LIJUAN - Chinese Academy Of Agricultural Sciences
item LI, HOUCHENG - Aarhus University
item TENG, JINYAN - South China Agricultural Univerisity
item WANG, ZHEN - Chinese Academy Of Agricultural Sciences
item QU, XIAOLU - Chinese Academy Of Agricultural Sciences
item CHEN, ZHE - Jiangsu Academy Agricultural Sciences
item CAI, XIAODIAN - South China Agricultural University
item ZENG, HAONAN - South China Agricultural Univerisity
item BAI, ZHONGHAO - Aarhus University
item LI, JINGHUI - University Of California, Davis
item PAN, XIANGCHUN - South China Agricultural Univerisity
item YAN, LEYAN - Jiangsu Academy Agricultural Sciences
item WANG, FEI - Aarhus University
item LIN, LIN - Aarhus University
item LUO, YONGLUN - Aarhus University
item SAHANA, GOUTAM - Aarhus University
item LUND, MOGENS SAND0 - Aarhus University
item BALLESTER, MARIA - Collaborator
item CRESPO-PIAZUELO, DANIEL - Collaborator
item KARLSKOV-MORTENSEN, PETER - University Of Copenhagen
item FREDHOLM, MERETE - University Of Copenhagen
item CLOP, ALEX - Collaborator
item AMILLS, MARCEL - Collaborator
item Loving, Crystal
item TUGGLE, CHRISTOPHER - Iowa State University
item MADSEN, OLE - Wageningen University And Research Center
item LI, JIAQI - South China Agricultural University
item ZHANG, ZHE - South China Agricultural Univerisity
item Liu, Ge
item JIANG, JICAI - North Carolina State University
item FANG, LINGZHAO - Aarhus University
item YI, GUOQIANG - Chinese Academy Of Agricultural Sciences

Submitted to: Advanced Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2025
Publication Date: 11/27/2025
Citation: Chen, L., Li, H., Teng, J., Wang, Z., Qu, X., Chen, Z., Cai, X., Zeng, H., Bai, Z., Li, J., Pan, X., Yan, L., Wang, F., Lin, L., Luo, Y., Sahana, G., Lund, M., Ballester, M., Crespo-Piazuelo, D., Karlskov-Mortensen, P., Fredholm, M., Clop, A., Amills, M., Loving, C.L., Tuggle, C.K., Madsen, O., Li, J., Zhang, Z., Liu, G., Jiang, J., Fang, L., Yi, G. 2025. Construction of a multitissue cell atlas reveals cell-type-specific regulation of molecular and complex phenotypes in pigs. Advanced Science. https://doi.org/10.1002/advs.202504961.
DOI: https://doi.org/10.1002/advs.202504961

Interpretive Summary: Comprehensive analyses of tissues at single-cell level will benefit our understanding of genetic bases for complex traits. We reported a single-cell atlas of adult pigs. These results fill our knowledge gaps and provide the foundation for incorporating new transcriptome insights into the future animal breeding program. Farmers, scientists, and policy planners who need to improve animal health and production based on genome-enabled animal selection will benefit from this study.

Technical Abstract: The systematic characterization of cellular heterogeneity among tissues and cell-type-specific regulation of complex phenotypes remains elusive in pigs. Within the Pig Genotype-Tissue Expression (PigGTEx) project, we present a single-cell 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 demonstrated 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 dissected 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 provided novel insights into cellular mechanisms behind these traits. Moreover, we highlighted that the heritability of human complex phenotypes was significantly enriched in orthologous genes with relevant cell-type-specific regulation in pigs. Altogether, our work provides a valuable resource for accelerating pig precision breeding and human biomedical research.