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

## TL;DR

This study creates a detailed cell atlas of pigs, revealing how different cell types regulate complex traits, aiding pig breeding and human research.

## Contribution

The study pioneers a multitissue cell atlas in pigs, linking cell-type-specific regulation to complex traits and human phenotypes.

## Key findings

- A single-cell transcriptome atlas of adult pigs was constructed with 229,268 nuclei from 19 tissues.
- Thousands of genetic variants with cell-type interaction effects on gene expression were identified.
- Cell-type-specific regulation in pigs shows heritability enrichment for human complex phenotypes.

## 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.

This research conducts an in‐depth investigation of cell‐type‐specific regulatory mechanisms underlying molecular and complex phenotypes through integrative analysis of multitissue single‐nucleus RNA sequencing, bulk RNA‐seq, and genome‐wide association study (GWAS) data in pigs. This pioneering study establishes a valuable genomic resource that significantly enhances pig precision breeding while simultaneously advancing human biomedical research.