小鼠孤雄单倍体胚胎干细胞增殖的研究

Study of Mouse Androgenetic Haploid Embryonic Stem Cells on Proliferation Ability

孤雄单倍体胚胎干细胞(androgenetic haploid embryonic stem cells,AG-ha ESCs)是来源于只具有一套精子染色体组的单倍体胚胎。小鼠AG-ha ESCs在培养中呈现克隆较小、生长缓慢的现象。该研究比较了小鼠AG-ha ESCs与正常二倍体胚胎干细胞(R1细胞)、二倍化后的AGha ESCs(DAG-ha ESCs)的生物学特征并探索其中的机制。结果表明,尽管小鼠AG-ha ESCs与R1细胞一样成集落样生长、边缘光滑清晰,但细胞大小与增殖速率均显著小于R1细胞;DAG-ha ESCs的增殖速率略高于AG-ha ESCs,但仍然显著低于R1。更为重要的是,通过RT-q PCR检测分析表明,AGha ESCs和DAG-ha ESCs细胞周期调控网络有异常,因此,单倍体基因组转录调控的异常是小鼠AGha ESCs增殖缓慢的关键因素,而不是克隆大小和二倍化。该研究为今后AG-ha ESCs细胞周期调控方面的进一步研究提供了良好的平台。

Androgenetic haploid embryonic stem cells （AG-haESCs）, which are derived from mouse hap- loid embryos with only a set of chromosomes from the spermatozoa, show small colony morphologies and hypo- proliferation properties during passages. Here, we compared AG-haESCs with the normal embryonic stem cells （R1） and diploidized AG-haESCs （DAG-haESCs） so as to uncover the mechanism. The result indicated that, although mouse AG-haESCs present colony-like morphologies with smooth and clear edge as normal ESCs, these colonies show smaller sizes as compared to R1. Moreover, the proliferation rates of AG-haESCs are dramatically down- regulated. Meanwhile, DAG-haESCs show a higher proliferation rate comparing to AG-haESCs, but which is still lower than R1. Importantly, RT-qPCR analysis demonstrated that both mouse AG-haESCs and DAG-haESCs pos- sess abnormal cell cycle related networks, suggesting that it is the transcriptional disorder by haploid chromosomes, but not the colony size or diploidization, plays a critical role in the proliferation regulation of these cells. Thus, our work provides a unique platform to further analyze the regulation of cell cycle regulation by AG-haESCs.