多能干细胞 z-bio 2024-12-24 532

　　Efficient differentiation scheme for venous endothelial cells (iVEC)

　　With the support of National Natural Science Foundation projects (approval numbers: 82370514, 82472171) and other grants, the teams of Researcher Wang Kai, Professor Kong Wei, Researcher Wang Qian, and Researcher Xie Zhengwei from Peking University have made progress in inducing pluripotent stem cells for vascular malformation modeling and drug discovery research. The research results, titled "Generation of iPSC derived human venous endothelial cells for modeling of vascular malformations and drug discovery", were published online on November 22, 2024 in the journal Cell Stem Cell. Paper link: https://www.sciencedirect.com/science/article/pii/S1934590924003771?via%3Dihub .

　　Venous malformations (VMs) are common vascular abnormalities, mainly caused by non genetic somatic mutations in venous endothelial cells (VECs). At present, there is a lack of mature models for VMs disease, which seriously hinders the discovery of drugs for treating VMs.

　　The research team has developed an efficient method for inducing induced venous endothelial cells (iVECs) in humans. Using gene editing technology, the L914F mutation was introduced into the TIE2 locus of induced pluripotent stem cells (iPSCs), and it was demonstrated that the mutated iVECs formed dilated blood vessels after transplantation into mice, thereby reproducing the phenotypic characteristics of VMs, including disrupted cytoskeleton, enhanced proliferation ability, and reduced luminal ability. In addition, the team conducted drug screening by combining deep neural networks with high-throughput digital RNA with perturbation of genes sequencing (DRUG seq) technology, and discovered a potential therapeutic drug for VMs, Bosutinib. By weakening the endothelial mesenchymal transition of mutant iVECs, inhibiting cell proliferation, and effectively improving the disease phenotype of VMs. The research team utilized genome editing and stem cell technology to construct a VMs disease model, laying the foundation for further development of novel drugs for treating VMs (Figure).