TRANSCRIPTOME DYNAMICS AND GENE REGULATORY NETWORKS DURING TESTIS DEVELOPMENT AND SPERMATOGENESIS IN CATTLE

While the current Cattle FAANG project excels in comprehensively understanding genomic regulatory elements in a wide-ranging set of adult and fetal cattle tissues, there is a significant knowledge gap regarding the regulatory dynamics of development and differentiation across the cattle lifecycle in each tissue, which determines economic traits in animal health and production. This study aims to fill this gap, focusing on male reproduction, which is imperative as the cattle industry relies on artificial insemination (AI) practices. The project comprises three specific aims: 1) Determine the temporal transcriptome dynamics and gene regulatory networks during bovine testis development, 2) Determine germ cell-specific transcriptome dynamics and gene regulatory networks in different germ cells during spermatogenesis, and 3) Determine the testis-biased genes and identify e/sQTL, as well as transcriptome-wide association studies (TWAS) of male fertility traits. To achieve these aims, we will annotate and integrate transcriptional profiles and chromatin states at a whole-genome level across the four developmental stages of testes and five different types of germ cells during spermatogenesis. Additionally, single-cell transcriptomics and chromatin states will provide insights into the regulatory dynamics of bovine germ cell differentiation events. Lastly, we will identify bull fertility-associated genomic variants within the annotated regulatory elements in the testis. TWAS with eVariants and colocalization of eQTLs and GWAS loci will enhance our ability to detect candidate causal genes for male fertility traits. This project is highly innovative, crucial, and significant for completing the bovine genome annotation and understanding the transcriptomics underlying testis development and spermatogenesis in ruminants.