IPGCA: A Comprehensive Single Cell Atlas of 1 074 127 Porcine Intestinal Cells Revealing Cellular Dynamics, Genetic Regulation, and Cross-Species Conservation.

The porcine intestinal tract is vital for nutrient absorption, immune regulation, and various physiological processes. However, a comprehensive understanding of its cellular composition and gene regulatory landscape remains limited. Here, the Integrated Pig Gut Cell Atlas (IPGCA) is presented, a comprehensive single cell resource comprising 1 074 127 cells spanning five intestinal segments, six developmental stages, and nine breeds. IPGCA enables the discovery of previously overlooked cell types (e.g., Paneth cells) and reveals dynamic B cell remodeling during weaning. Combining with genome-wide association studies (GWAS), complex traits are linked to potential causal cell types. Furthermore, the utility of IPGCA as a reference for the deconvolution of bulk RNA-seq data is demonstrated, enabling the identification of cell type interaction expression quantitative trait loci (ieQTLs) and deconvolutional eQTLs (decon-eQTL). Co-localization analyses implicate enterocyte BNC2 functions in loin muscle area trait and endothelial cell BAG3 in backfat thickness. Strikingly, comparative analysis with human intestinal atlases reveals a high degree of conservation, reinforcing the pig's value as a model for human gut biology. To empower the community, scGutDB (http://alphaindex.zju.edu.cn/scgut) is developed, an interactive platform for data exploration. IPGCA provides a foundational resource for agricultural genomics, precision breeding, and translational studies of intestinal physiology and diseases.