提高注射胚胎中的细胞存活率可使已重编程的多能干细胞生成嵌合食蟹猴。
Improving Cell Survival in Injected Embryos Allows Primed Pluripotent Stem Cells to Generate Chimeric Cynomolgus Monkeys.
机构信息
Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Provincial Academy of Science and Technology, Kunming, Yunnan 650500, China.
Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Provincial Academy of Science and Technology, Kunming, Yunnan 650500, China; Kunming Enovate Institute of Bioscience, Kunming, Yunnan 650500, China.
出版信息
Cell Rep. 2018 Nov 27;25(9):2563-2576.e9. doi: 10.1016/j.celrep.2018.11.001.
Monkeys are an optimal model species for developing stem cell therapies. We previously reported generating chimeric cynomolgus monkey fetuses using dome-shaped embryonic stem cells (dESCs). However, conventional primed pluripotent stem cells (pPSCs) lack chimera competency. Here, by altering the media in which injected morulae are cultured, we observed increased survival of cynomolgus monkey primed ESCs, induced PSCs, and somatic cell nuclear transfer-derived ESCs, thereby enabling chimeric contributions with 0.1%-4.5% chimerism into the embryonic and placental tissues, including germ cell progenitors in chimeric monkeys. Mechanically, dESCs and pPSCs belong to different cell types and similarly express epiblast ontogenic genes. The host embryonic microenvironment could reprogram injected PSCs to embryonic-like cells. However, the reprogramming level and chimerism were associated with the cell state of injected PSCs. Our findings provide a method to understand pluripotency and broaden the use of embryonic chimeras for basic developmental biology research and regenerative medicine.
猴子是开发干细胞治疗的最佳模式生物。我们之前曾报道过使用穹顶状胚胎干细胞（dESC）生成嵌合食蟹猴胚胎。然而，传统的初始多能干细胞（pPSC）缺乏嵌合能力。在这里，通过改变注射桑椹胚培养的培养基，我们观察到食蟹猴初始 ESC、诱导 PSC 和体细胞核移植衍生 ESC 的存活率增加，从而使嵌合贡献达到 0.1%-4.5%的嵌合率进入胚胎和胎盘组织，包括嵌合猴中的生殖细胞祖细胞。从机制上讲，dESC 和 pPSC 属于不同的细胞类型，并且相似地表达胚层发生基因。宿主胚胎微环境可以将注射的 PSC 重编程为胚胎样细胞。然而，重编程水平和嵌合率与注射的 PSC 细胞状态有关。我们的研究结果提供了一种理解多能性的方法，并拓宽了胚胎嵌合体在基础发育生物学研究和再生医学中的应用。
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