New insights into Vitamin C function: Vitamin C induces JAK2 activation through its receptor-like transporter SVCT2.

Vitamin C (VitC) is a requisite nutrient for humans and other primates. Extensive research continuously illustrates the applications of VitC in promoting cell reprogramming, fine-tuning embryonic stem cell function, and fighting diseases. Given its chemical reduction property, VitC predominantly acts as an antioxidant to reduce reactive oxygen species (ROS) and as a cofactor for certain dioxygenases involved in epigenetic regulation. Here, we propose that VitC is also a bio-signaling molecule based on the finding that sodium-dependent VitC transporter (SVCT) 2 is a novel receptor-like transporter of VitC that possesses dual activities in mediating VitC uptake and Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 2 signaling pathway. Through interaction, SVCT2 induces JAK2 phosphorylation while transporting VitC into cells. Activated JAK2 phosphorylates the C-terminus of SVCT2, resulting in the recruitment and activation of STAT2. As a highlight, our results suggest that the activation of JAK2 synergistically promotes regulation of VitC in ROS scavenging and epigenetic modifications through phosphorylating pyruvate dehydrogenase kinase 1, ten-eleven translocation enzyme 3, and histone H3 Tyr41. Furthermore, VitC-activated JAK2 exhibits bidirectional effects in regulating cell pluripotency and differentiation. Our results thus reveal that the SVCT2-mediated JAK2 activation facilitates VitC functions in a previously unknown manner.

Transcriptome Analyses Reveal Effects of Vitamin C-Treated Donor Cells on Cloned Bovine Embryo Development.

Somatic cell nuclear transfer (SCNT) is a very powerful technique used to produce genetically identical or modified animals. However, the cloning efficiency in mammals remains low. In this study, we aimed to explore the effects of vitamin C (Vc)-treated donor cells on cloned embryos. As a result, Vc treatment relaxed the chromatin of donor cells and improved cloned embryo development. RNA sequencing was adopted to investigate the changes in the transcriptional profiles in early embryos. We found that Vc treatment increased the expression of genes involved in the cell-substrate adherens junction. Gene ontology (GO) analysis revealed that Vc treatment facilitated the activation of autophagy, which was deficient in cloned two-cell embryos. Rapamycin, an effective autophagy activator, increased the formation of cloned blastocysts (36.0% vs. 25.6%, p < 0.05). Abnormal expression of some coding genes and long non-coding RNAs in cloned embryos was restored by Vc treatment, including the zinc-finger protein 641 (ZNF641). ZNF641 compensation by means of mRNA microinjection improved the developmental potential of cloned embryos. Moreover, Vc treatment rescued some deficient RNA-editing sites in cloned two-cell embryos. Collectively, Vc-treated donor cells improved the development of the cloned embryo by affecting embryonic transcription. This study provided useful resources for future work to promote the reprogramming process in SCNT embryos.