No abstract

Detailed molecular studies of preimplantation stage development in a suitable nonhuman primate model organism have been inhibited due to the cost and scarcity of embryos. To circumvent these limitations, we have created a new resource for the research community, designated as the Primate Embryo Gene Expression Resource (PREGER). The PREGER sample collection currently contains over 160 informative samples of oocytes, obtained from various sized antral follicles, and embryos obtained through a variety of different protocols. The PREGER makes it possible to undertake quantitative gene-expression studies in rhesus monkey oocytes and embryos through simple and cost-effective hybridization-based methods. The PREGER also makes available other molecular tools to facilitate nonhuman primate embryology. We used PREGER here to compare the temporal expression patterns of five housekeeping mRNAs and three transcription factor mRNAs between mouse and rhesus monkey. We observed noticeable differences in temporal expression patterns between species for some mRNAs, but clear similarities for others. Our results also provide new information related to genome activation and the effects of embryo culture conditions on gene expression in primate embryos. These results provide one illustration of how the PREGER can be employed to obtain novel insight into primate embryogenesis.

VEGFR2 (KDR/Flk1) signaling in endothelial cells (ECs) is essential for developmental and reparative angiogenesis. Reactive oxygen species (ROS) and copper (Cu) are also involved.in these processes. However, their inter-relationship is poorly understood. The role of endothelial Cu importer CTR1 in VEGFR2 signaling and angiogenesis in vivo is hitherto unknown. Here we show that CTR1 functions as a previously unrecognized redox sensor to promote angiogenesis in ECs. CTR1-depleted ECs showed reduced VEGF-induced VEGFR2 signaling and angiogenic responses. Mechanistically, CTR1 was rapidly sulfenylated at Cys189 in cytosolic C-terminus upon VEGF stimulation, which induced CTR1-VEGFR2 disulfide bond formation and their co-internalization to early endosomes, driving sustained VEGFR2 signaling. In vivo , EC-specific Ctr1-deficient mice or CRISPR/Cas9-generated “redox-dead” Cys to Ala Ctr1 knock-in mutant mice had impaired developmental and reparative angiogenesis. Thus, oxidation of CTR1 at Cys189 promotes VEGFR2 internalization and signaling to enhance angiogenesis. Our study uncovers an important mechanism for ROS sensing through CTR1 to drive neovascularization.