Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj 211002, India; Institute of Biomedicine, University of Eastern Finland, FI-70210 Kuopio, Finland.
Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj 211002, India.
Stem Cell Res. 2021 May;53:102334. doi: 10.1016/j.scr.2021.102334. Epub 2021 Apr 8.
Pluripotent stem cells (PSCs) have been observed to occur in two distinct states - naive and primed. Both naive and primed state PSCs can give rise to tissues of all the three germ layers in vitro but differ in their potential to generate germline chimera in vivo. Understanding the molecular mechanisms that govern these two states of pluripotency in human can open a plethora of opportunities for studying early embryonic development and in biomedical applications. In this work, we use weighted gene co-expression network analysis (WGCNA) to identify the key molecular makers and their interactions that define the two distinct pluripotency states. Signed hybrid network was reconstructed from transcriptomic data (RNA-seq) of naive and primed state pluripotent samples. Our analysis revealed two sets of genes that are involved in the establishment and maintenance of naive and primed states. The naive state genes were found to be enriched for biological processes and pathways related to metabolic processes while primed state genes were associated with system development. We further filtered these lists to identify the intra-modular hubs and the hub transcription factors (TFs) for each group. Validation of the identified TFs was carried out using independent microarray datasets and we finally present a list of 52 and 33 TFs as the set of core TFs that are responsible for the induction and maintenance of naive and primed states of pluripotency in human, respectively. Among these, the TFs ZNF275, ZNF232, SP4, and MSANTD3 could be of interest as they were not reported in previous studies.
多能干细胞（PSCs）被观察到存在两种不同的状态——原始态和起始态。原始态和起始态 PSCs 都可以在体外产生三个胚层的组织，但在体内生成种系嵌合体的潜力上有所不同。了解调控人类这两种多能性状态的分子机制，可以为研究早期胚胎发育和生物医学应用开辟大量机会。在这项工作中，我们使用加权基因共表达网络分析（WGCNA）来识别定义这两种不同的多能性状态的关键分子标记及其相互作用。从原始态和起始态多能性样本的转录组数据（RNA-seq）中重建了有向混合网络。我们的分析揭示了两组基因，它们参与原始态和起始态的建立和维持。原始态基因被发现富集于与代谢过程相关的生物学过程和途径，而起始态基因与系统发育相关。我们进一步筛选这些列表，以确定每个组的模块内枢纽基因和枢纽转录因子（TFs）。使用独立的微阵列数据集对鉴定的 TFs 进行验证，我们最终提出了一组 52 个和 33 个 TFs，分别作为诱导和维持人类原始态和起始态多能性的核心 TFs 集。其中，ZNF275、ZNF232、SP4 和 MSANTD3 等 TFs 可能具有研究意义，因为它们在以前的研究中没有报道过。
