Striking Similarity in the Gene Expression Levels of Individual Myc Module Members among ESCs, EpiSCs, and Partial iPSCs

Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs). Epiblast stem cells (EpiSCs) are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs) and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties.

已有的研究证实，三类核心转录调控子网——核心模块（Core）、Myc模块与PRC模块——参与维持胚胎干细胞（embryonic stem cells, ESCs）的多能性与自我更新能力。上胚层干细胞（epiblast stem cells, EpiSCs）是另一类具备多能性与自我更新能力的细胞类型。然而截至目前，上述三类模块在上胚层干细胞中的功能尚未得到系统性研究。本研究中，我们对比了胚胎干细胞与上胚层干细胞中核心、Myc及PRC模块基因的平均表达水平。相较于胚胎干细胞，上胚层干细胞的PRC模块基因表达水平显著升高，而核心模块基因表达水平则显著降低；与此同时，Myc模块基因的平均表达水平几乎无差异。后续分析显示，这两类细胞中Myc模块的基因表达相似性并非仅体现在整体层面，即便对单个基因的表达进行比较，也能观察到显著的相似性。我们还观察到，诱导多能干细胞（induced pluripotent stem cells, iPSCs）与部分诱导多能干细胞（partial iPSCs，即诱导多能干细胞诱导过程中产生的非目标副产物）之间，单个Myc模块基因的表达相似性水平同样相当。此外，本研究数据证实，部分诱导多能干细胞的自我更新特性依赖于高水平的c-Myc表达。