Abnormal Epigenetic Modifications in Surviving Somatic Cell Cloned Cattle Associated With Donor Cell Type

Background Studies have shown that the efficiency of somatic cell nuclear transfer (SCNT) is related to the type of donor cell used. Previous studies have shown that fetal oviduct epithelial cells (FOVs) exhibit a higher blastocyst formation rate than fetal fibroblasts (FFBs), but they are associated with lower pregnancy, calving, and full-term rates after implantation. The reason for this difference is unclear. Result In this study, we performed the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA-seq, and 5-hydroxymethylcytidine (5hmC) and 5-methylcytosine (5mC) DNA methylation sequencing methods across the whole genome to analyze the epigenetic differences between cattle cloned using FFBs or FOVs as donor nuclei. The results showed that chromatin openness, gene expression levels, and 5hmC contents were greater in cloned cattle derived from FOV donor nuclei than in those derived from FFBs. ATAC-seq and RNA-seq analyses of cloned bovine ear tissues derived from the same source of donor nuclei showed an obvious clustering tendency. In this study, we also found that the 5hmC content of surviving cloned cattle derived from FFBs was greater than 4‰, whereas it was less than 2‰ in dead cloned cattle. Conclusion We found that there were abnormalities in specific epigenetic modifications and gene expression in living somatic cell cloned cattle derived from different donor nuclei. Although cloned cattle undergo somatic reprogramming and differentiation, they retain the epigenetic imprints of their donor nuclei, and this somatic imprinting may affect the development rate of cloned blastocysts as well as the birth rate and development status of cloned fetuses after implantation.