诱导ETV2缺失的猪胚胎产生人内皮，这一成果由美国明尼苏达大学Daniel J. Garry和Mary G. Garry课题组合作经过不懈努力而取得。该研究成果在线发表在2020年2月24日出版的《自然-生物技术》杂志上。

研究人员使用基因编辑和体细胞核移植方法来改造ETV2缺失的猪胚胎，ETV2是血管内皮谱系的主控调节因子。ETV2缺失的猪胚胎缺乏血内皮细胞，并具有胚胎致死性。ETV2缺失的胚泡与野生型猪卵裂球胚泡互补产生了可存活的嵌合胚胎，其血管内皮细胞完全是供体来源的。在ETV2缺失的胚泡中注射人诱导多能干细胞（hiPSC）或过量表达抗凋亡因子BCL2的hiPSC，将这些细胞转移至代孕母猪中并在胚胎发育的第17天和第18天之间进行分析。研究人员发现在这些胚胎中，所有内皮细胞都是人类起源的。

据了解，将来可以通过使用猪来培养人源化器官，从而解决供体器官短缺的问题，并且人源化器官在移植后具有较低的人类免疫排斥反应。先前的研究表明，发育调控基因缺失的啮齿动物胚泡的种间互补可以产生异种胰腺和肾脏。但是，这些器官含有的宿主内皮是免疫排斥的主要来源。

附：英文原文

Title: Generation of human endothelium in pig embryos deficient in ETV2

Author: Satyabrata Das, Naoko Koyano-Nakagawa, Ohad Gafni, Geunho Maeng, Bhairab N. Singh, Tara Rasmussen, Xiaoyan Pan, Kyung-Dal Choi, Daniel Mickelson, Wuming Gong, Pruthvi Pota, Cyprian V. Weaver, Stefan Kren, Jacob H. Hanna, Demetris Yannopoulos, Mary G. Garry, Daniel J. Garry

Issue&Volume: 2020-02-24

Abstract: The scarcity of donor organs may be addressed in the future by using pigs to grow humanized organs with lower potential for immunological rejection after transplantation in humans. Previous studies have demonstrated that interspecies complementation of rodent blastocysts lacking a developmental regulatory gene can generate xenogeneic pancreas and kidney1,2. However, such organs contain host endothelium, a source of immune rejection. We used gene editing and somatic cell nuclear transfer to engineer porcine embryos deficient in ETV2, a master regulator of hematoendothelial lineages3,4,5,6,7. ETV2-null pig embryos lacked hematoendothelial lineages and were embryonic lethal. Blastocyst complementation with wild-type porcine blastomeres generated viable chimeric embryos whose hematoendothelial cells were entirely donor-derived. ETV2-null blastocysts were injected with human induced pluripotent stem cells (hiPSCs) or hiPSCs overexpressing the antiapoptotic factor BCL2, transferred to synchronized gilts and analyzed between embryonic day 17 and embryonic day 18. In these embryos, all endothelial cells were of human origin.

DOI: 10.1038/s41587-019-0373-y

Source: https://www.nature.com/articles/s41587-019-0373-y