Reduced diploidization and survival improvement of semi-cloned mice produced from androgenetic haploid embryonic stem cells. Mus musculus

We found that the overall DNA methylation and hydroxymethylation in AG-haESCs are extremely low, and the downregulation of both de novo methyltransferase Dnmt3b and methylation maintenance enzyme Dnmt1was discovered responsible for this DNA hypomethylation. Further, our study discovered that the correction of DNA methylation can greatly reduce the incidence of diploidization and further improve the survival of semi-cloned mice produced from AG-haESCs. Overall design: Gene expression profiles by RNA-Seq were analyzed to investigate transcriptional changes between AG-haESCs and other samples. Transcriptional profiling of 2i cultured ESC XX.

本研究发现，孤雄单倍体胚胎干细胞（AG-haESCs）整体的DNA甲基化与DNA羟甲基化水平极低，且从头甲基转移酶Dnmt3b与甲基化维持酶Dnmt1的共同下调是引发该DNA低甲基化现象的原因。进一步研究表明，校正DNA甲基化水平可显著降低AG-haESCs诱导的二倍体化发生率，并进一步提升由AG-haESCs产生的半克隆小鼠的存活率。
总体实验设计：通过RNA测序（RNA-Seq）分析基因表达谱，以探究AG-haESCs与其他样本间的转录组差异；同时对2i培养的XX型胚胎干细胞进行转录组分析。