Validation of Baboon Pluripotent Cells as a Model for Translational Stem Cell Research [ChIP-Seq]. Validation of Baboon Pluripotent Cells as a Model for Translational Stem Cell Research [ChIP-Seq]

To investigate the extent of similarity in epigenetic programming among human, baboon and mouse PSCs, we examined genome-wide patterns of four chromatin modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac) and DNA methylation in baboon iPSC and ESCs. We show that baboon pluripotent cells (PSCs) recapitulate key molecular features of human PSCs with much greater accuracy than that found in PSCs from non-primate species. Specifically, baboon and human PSCs exhibit significantly greater conservation of gene expression patterns, higher sequence and structural homology among pluripotency factors, more equivalent genome-wide patterns of histone and DNA methylation modifications, and similar maintenance of bivalent programming of developmental genes than that found between human and non-primate PSCs. Overall design: Examination of transcriptome, H3K4me3, H3K27ac, H3K9me3, H3K27me3 and DNA methylation in baboon iPSC and ESC.

为探究人类、狒狒与小鼠多能干细胞（PSCs）的表观遗传编程相似性程度，我们针对狒狒诱导多能干细胞（iPSC）与胚胎干细胞（ESCs）的四种染色质修饰（H3K4me3、H3K9me3、H3K27me3、H3K27ac）的全基因组分布模式以及DNA甲基化水平开展了检测分析。研究表明，狒狒多能干细胞（PSCs）所重现的人类多能干细胞关键分子特征，其契合程度远高于非灵长类多能干细胞与人类多能干细胞的契合度。具体而言，相较于人类与非灵长类多能干细胞的对比结果，狒狒与人类多能干细胞在基因表达模式的保守性上显著更强，多能性因子的序列与结构同源性更高，组蛋白与DNA甲基化修饰的全基因组分布模式更为一致，且对发育基因的二价编程维持机制也更为相似。整体实验设计：对狒狒诱导多能干细胞与胚胎干细胞的转录组、H3K4me3、H3K27ac、H3K9me3、H3K27me3以及DNA甲基化水平进行检测分析。