Molecular Signatures and Networks of Cardiomyocyte Differentiation in Humans and Mice
Molecular Signatures and Networks of Cardiomyocyte Differentiation in Humans and Mice
复制标题
人类和小鼠心肌细胞分化的分子特征和网络
DOI：
10.1016/j.omtn.2020.07.011
复制
发表时间：
2020-09-04
期刊：
影响因子：
--
通讯作者：
Li, Li
中科院分区：
文献类型：
--
作者：
Wang, Yumei;Yi, Na;Li, Li
胚胎干细胞（ESCs）衍生的心肌细胞分化是一个涉及多个水平分子调控的复杂过程。在这项研究中，我们首先识别并比较了人类和小鼠内皮细胞来源的心肌细胞分化（ESCDCD）的差异表达基因（DEG）特征。然后，对人类ESCDCD数据集进行多尺度嵌入式基因共表达网络分析（MEGENA），鉴定出212个显著共表达的基因模块，这些基因模块很好地捕获了心肌细胞分化的调控信息。干细胞多能性、Wnt和钙通路调控的三个模块在两种物种分化相变的DEG信号中都有富集。确定了三种人类特异性心肌细胞分化相变模块。此外，还阐述了转录因子在心肌细胞分化过程中的潜在调控机制。最后，通过小鼠胚胎心肌细胞分化过程中ESCDCD的表达，确定了几个新的关键驱动因素。利用综合网络分析，在人类和小鼠中确定了心肌细胞谱系承诺的核心分子特征和基因子网络（模块）。我们的研究结果提供了基因共调控的全球图景，并确定了ESCDCD过程中的关键调控因子。
Cardiomyocyte differentiation derived from embryonic stem cells (ESCs) is a complex process involving molecular regulation of multiple levels. In this study, we first identify and compare differentially expressed gene (DEG) signatures of ESC-derived cardiomyocyte differentiation (ESCDCD) in humans and mice. Then, the multiscale embedded gene co-expression network analysis (MEGENA) of the human ESCDCD dataset is performed to identify 212 significantly co-expressed gene modules, which capture well the regulatory information of cardiomyocyte differentiation. Three modules respectively involved in the regulation of stem cell pluripotency, Wnt, and calcium pathways are enriched in the DEG signatures of the differentiation phase transition in the two species. Three human-specific cardiomyocyte differentiation phase transition modules are identified. Moreover, the potential regulation mechanisms of transcription factors during cardiomyocyte differentiation are also illustrated. Finally, several novel key drivers of ESCDCD are identified with the evidence of their expression during mouse embryonic cardiomyocyte differentiation. Using an integrative network analysis, the core molecular signatures and gene subnetworks (modules) underlying cardiomyocyte lineage commitment are identified in both humans and mice. Our findings provide a global picture of gene-gene co-regulation and identify key regulators during ESCDCD.