黄粤课题组在《Cell Discovery》 杂志发表研究论文“Rapidly Generating Knockout Mice from H19-Igf2 Engineered Androgenetic Haploid Embryonic Stem Cells （2015）”。

      通过人为修正AH-ES 细胞中的H19-Igf2 印记基因座，使得其维持稳定的基因组印记状态，可高效获得遗传修饰SC小鼠的能力。中国医学科学院基础医学研究所，“医学分子生物学国家重点实验室”的黄粤课题组利用CRISPR-Cas9 辅助的高效同源重组技术，在小鼠孤雄单倍体胚胎干细胞中对H19-Igf2 印记基因座进行修饰，由此得到“类精子”的新型细胞系，可用于快速高效地制作基因修饰小鼠，是一种新的生物技术。

      【摘要】：Haploid mammalian embryonic stem cells (ESCs) hold great promise for functional genetic studies and assisted reproduction. Recently, rodent androgenetic haploid ESCs (AG-haESCs) were generated from androgenetic blastocysts and functioned like sperm to produce viable offspring via the intracytoplasmic AG-haESCs injection into oocytes. However, the efficiency of this reproduction was very low. Most pups were growth-retarded and died shortly after birth, which is not practical for producing knockout animals. Further investigation suggested a possible link between the low birthrate and aberrant expression of imprinted genes. Here, we report the high-frequency generation of healthy, fertile mice from H19-Igf2 imprinting-locus modified AG-haESCs, which maintained normal paternal imprinting and pluripotency. Moreover, it is feasible to perform further genetic manipulations in these AG-haESCs. Our study provides a reliable and

efficient tool to rapidly produce gene-modified mouse models and will benefit reproductive medicine in the future.

      相关结果已发表于《Cell Discovery》 杂志（2015，1: e15031），其作者为黄粤课题组博士研究生张美丽，刘语方，刘光，重点室黄粤研究员是本文的通讯作者。该研究工作得到了以下基金的支持：National Natural Science Foundation of China (91231111 to YH)。