Li Xu, Peng Keli, Zhang Jinxin, Gao Qian, Zhang Wenhao, Hua Ruotong, Shuai Ling
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300350, China.
Sheng Wu Gong Cheng Xue Bao. 2019 May 25;35(5):910-918. doi: 10.13345/j.cjb.180506.
Parthenogenetic embryonic stem cells (pESCs) derived from bi-maternal genomes do not have competency of tetraploid complementation, due to lacking of paternal imprinting genes. To make pESCs possess fully development potentials and similar pluripotency to zygote-derived ESCs, we knocked out one allelic gene of the two essential maternal imprinting genes (H19 and IG) in their differentially methylated regions (DMR) via CRISPR/Cas9 system and obtained double knock out (DKO) pESCs. Maternal pESCs had similar morphology, expression levels of pluripotent makers and in vitro neural differentiation potentials to zygotes-derived ESCs. Besides that, DKO pESCs could contribute to full-term fetuses through tetraploid complementation, proving that they held fully development potentials. Derivation of DKO pESCs provided a type of major histocompatibility complex (MHC) matched pluripotent stem cells, which would benefit research in regenerative medicine.
来自双母体基因组的孤雌生殖胚胎干细胞（pESC）由于缺乏父本印记基因，不具备四倍体互补能力。为了使pESC具有完全的发育潜能和与合子来源的胚胎干细胞相似的多能性，我们通过CRISPR/Cas9系统在两个必需的母体印记基因（H19和IG）的差异甲基化区域（DMR）敲除了一个等位基因，获得了双敲除（DKO）pESC。母体pESC在形态、多能性标志物表达水平和体外神经分化潜能方面与合子来源的胚胎干细胞相似。除此之外，DKO pESC可通过四倍体互补产生足月胎儿，证明它们具有完全的发育潜能。DKO pESC的获得提供了一种主要组织相容性复合体（MHC）匹配的多能干细胞，这将有利于再生医学研究。
