Integrative single-cell RNA-seq and ATAC-seq analysis of myogenic differentiation in pig.

BACKGROUND: Skeletal muscle development is a multistep process whose understanding is central in a broad range of fields and applications, from the potential medical value to human society, to its economic value associated with improvement of agricultural animals. Skeletal muscle initiates in the somites, with muscle precursor cells generated in the dermomyotome and dermomyotome-derived myotome before muscle differentiation ensues, a developmentally regulated process that is well characterized in model organisms. However, the regulation of skeletal muscle ontogeny during embryonic development remains poorly defined in farm animals, for instance in pig. Here, we profiled gene expression and chromatin accessibility in developing pig somites and myotomes at single-cell resolution. RESULTS: We identified myogenic cells and other cell types and constructed a differentiation trajectory of pig skeletal muscle ontogeny. Along this trajectory, the dynamic changes in gene expression and chromatin accessibility coincided with the activities of distinct cell type-specific transcription factors. Some novel genes upregulated along the differentiation trajectory showed higher expression levels in muscular dystrophy mice than that in healthy mice, suggesting their involvement in myogenesis. Integrative analysis of chromatin accessibility, gene expression data, and in vitro experiments identified EGR1 and RHOB as critical regulators of pig embryonic myogenesis. CONCLUSIONS: Collectively, our results enhance our understanding of the molecular and cellular dynamics in pig embryonic myogenesis and offer a high-quality resource for the further study of pig skeletal muscle development and human muscle disease.

Utilizing Variants Identified with Multiple Genome-Wide Association Study Methods Optimizes Genomic Selection for Growth Traits in Pigs.

Improving the prediction accuracies of economically important traits in genomic selection (GS) is a main objective for researchers and breeders in the livestock industry. This study aims at utilizing potentially functional SNPs and QTLs identified with various genome-wide association study (GWAS) models in GS of pig growth traits. We used three well-established GWAS methods, including the mixed linear model, Bayesian model and meta-analysis, as well as 60K SNP-chip and whole genome sequence (WGS) data from 1734 Yorkshire and 1123 Landrace pigs to detect SNPs related to four growth traits: average daily gain, backfat thickness, body weight and birth weight. A total of 1485 significant loci and 24 candidate genes which are involved in skeletal muscle development, fatty deposition, lipid metabolism and insulin resistance were identified. Compared with using all SNP-chip data, GS with the pre-selected functional SNPs in the standard genomic best linear unbiased prediction (GBLUP), and a two-kernel based GBLUP model yielded average gains in accuracy by 4 to 46% (from 0.19 ± 0.07 to 0.56 ± 0.07) and 5 to 27% (from 0.16 ± 0.06 to 0.57 ± 0.05) for the four traits, respectively, suggesting that the prioritization of preselected functional markers in GS models had the potential to improve prediction accuracies for certain traits in livestock breeding.