PRDM14 promotes the bovine somatic stem cell reprogramming through enhancing oxidative phosphorylation at the initial stage.

Bovine induced pluripotent stem cells (biPSCs), which can be obtained through somatic cells reprogramming have multiple potential applications in human disease, regeneration medicine and biotechnical animal breeding. However, the low reprogramming efficiency and poorly exploration of the mechanism underlying the somatic cells reprogramming in cattle restricted the applications of biPSCs. Here, we reported the transcription factor PR-domain containing protein 14 (PRDM14) was highly expressed in bovine fetal testis and intestine. And the expression of PRDM14 showed the lowest level in bovine embryonic fibroblasts (BEF), increased on day 3 and day 18, and finally reached the highest level in induced pluripotent stem cells (iPSCs) during the reprogramming induced by OCT4, SOX2, KLF4 and MYC (OSKM). In a gain-of-function assay, we showed that PRDM14 was able to enhance the efficiency of reprogramming from BEF in conjunction with bovine OSKM. While, silencing of PRDM14 inhibited the reprogramming efficiency of BEF. The bovine iPSCs derived from OSKM plus PRDM14 displayed normal karyotype, expressed pluripotent markers and could differentiated into three germ layers in vitro. Transcriptome analysis of cells at the early, median and late reprogramming stages revealed that several genes involved in oxidative phosphorylation (OXPHOS) are upregulated on day 3 when OXPHOS burst occurs, while downregulated on day 15 when OXPHOS transmits to glycolysis, by ectopic expression of PRDM14. RT-qPCR and ATP content detection further confirmed that PRDM14 could improve somatic cells reprogramming by enhancing OXPHOS at the early stage. Additionally, forced expression of PRDM14 in OSKM-induced biPSCs showed that it upregulates the expression of key pluripotency gene NANOG but downregulates LIN28, DNA methylation genes DNMT1/3B and DNA demethylation genes TET1/2/3. Altogether, our study uncovers PRDM14 exemplifies a key transcription factor required for the reacquisition of pluripotency in bovine somatic cells and the maintenance of bovine iPSCs identity.