Ha Misook, Hong Soondo
Samsung Advanced Institute of Technology, Samsung Electronics Corporation, Suwon 443-803, Korea.
Department of Industrial Engineering, Pusan National University, Busan 46241, South Korea.
Nucleic Acids Res. 2017 Oct 13;45(18):10428-10435. doi: 10.1093/nar/gkx752.
Pluripotency, the ability of embryonic stem cells to differentiate into specialized cell types, is determined by ESC-specific gene regulators such as transcription factors and chromatin modification factors. It is not well understood how ESCs are poised for differentiation, however, and methods are needed for prognosis of the molecular changes in the differentiation of ESCs into specific organs. We describe a new approach to infer cell-type specific gene regulatory programs based on gene regulatory interactions in ESCs. Our method infers the molecular logic of gene regulatory mechanisms by mapping the position-specific combinatory patterns of numerous regulators in ESCs into cell-type specific gene regulations. We validate the proposed approach by recapitulating the RNA-seq and microarray data of neuronal progenitor cells, adult liver cells, and ESCs from the integrated patterns of diverse gene regulators in ESCs. We find that the collective functions of diverse gene regulators in ESCs represent distinct gene regulatory programs in specialized cell types. Our new approach expands our understanding of the differential gene regulatory information in developments encoded in regulatory networks of ESCs.
多能性，即胚胎干细胞分化为特定细胞类型的能力，由胚胎干细胞特异性基因调节因子决定，如转录因子和染色质修饰因子。然而，目前尚不清楚胚胎干细胞如何为分化做好准备，并且需要一些方法来预测胚胎干细胞分化为特定器官过程中的分子变化。我们描述了一种基于胚胎干细胞中的基因调控相互作用来推断细胞类型特异性基因调控程序的新方法。我们的方法通过将胚胎干细胞中众多调节因子的位置特异性组合模式映射到细胞类型特异性基因调控中，来推断基因调控机制的分子逻辑。我们通过从胚胎干细胞中不同基因调节因子的整合模式中重现神经元祖细胞、成体肝细胞和胚胎干细胞的RNA测序和微阵列数据，来验证所提出的方法。我们发现胚胎干细胞中不同基因调节因子的集体功能代表了特定细胞类型中不同的基因调控程序。我们的新方法扩展了我们对胚胎干细胞调控网络中编码的发育过程中差异基因调控信息的理解。
