Key genes and integrated modules in hematopoietic differentiation of human embryonic stem cells: a comprehensive bioinformatic analysis.-猫眼课题宝

人胚胎干细胞造血分化的关键基因和整合模块：综合生物信息分析

DOI：

10.1186/s13287-018-1050-7

发表时间：

2018-11-08

期刊：

Stem cell research & therapy

影响因子：

7.5

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Li P;Wu M;Lin Q;Wang S;Chen T;Jiang H

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225692/

背景从人胚胎干细胞(HESCs)获得造血干细胞(HSCs)和血细胞是再生医学的主要目标，但其分化机制在很大程度上尚不清楚。本研究旨在通过生物信息学的综合分析，寻找与EHT早期分化相关的调控基因和功能模块。方法分离和收集未分化的人胚胎干细胞(hESC-H9)、分化10天的hESC-H9的CD34+细胞和脐带细胞的CD34+细胞。对3组细胞进行RNA提取和微阵列分析，采用基因芯片显著性分析(SAM)和短时间序列表达挖掘(STEM)算法分析差异表达基因(DEG)和时间序列图谱。利用RSTUDIO中的ClusterProfilerPackage进行基因浓缩分析，利用搜索工具构建蛋白质-蛋白质相互作用(PPI)网络，检索相互作用基因(字符串)，并在Cytoscape中可视化。结果在本研究中，我们鉴定出在染色体分离、细胞周期、白细胞激活和分化以及造血等生物学过程中富含HUB基因的11,262个deg和16个时间序列图谱。MCODE算法分析进一步确定了可能在EHT过程中发挥重要作用的6个整合模块，包括有丝分裂/细胞周期、线粒体过程、剪接、泛素化、核糖体和凋亡。结论本研究发现了与人ESCs造血和内皮分化相关的潜在基因和整合功能模块。

BackgroundThe generation of hematopoietic stem cells (HSCs) and blood cells from human embryonic stem cells (hESCs) is a major goal for regenerative medicine; however, the differentiation mechanisms are largely undefined. Here, we aimed to identify the regulated genes and functional modules related to the early differentiation of the endothelial-to-hematopoietic transition (EHT) using comprehensive bioinformatics analyses.MethodsUndifferentiated hESCs (hESC-H9), CD34+cells from 10-day differentiated hESC-H9 cells, and CD34+cells from umbilical cord cells were isolated and collected. Cells from these three groups were subjected to RNA extraction and microarray analysis by which differentially expressed genes (DEGs) and time-series profiles were analyzed by significance analysis of microarray (SAM) and short time-series expression miner (STEM) algorithms. Gene enrichment analysis was performed byClusterProfilerPackage inRstudio, while a protein-protein interaction (PPI) network was constructed by search tool for the retrieval of interacting genes (STRING) and visualized in Cytoscape. Hub genes were further identified with the MCODE algorithm in Cytoscape.ResultsIn the present study, we identified 11,262 DEGs and 16 time-series profiles that were enriched in biological processes of chromosome segregation, cell cycle, and leukocyte activation and differentiation, as well as hematopoiesis. Analysis using the MCODE algorithm further identified six integrated modules that might play an important role in the EHT process, including mitosis/cell cycle, mitochondrial process, splicing, ubiquitination, ribosome, and apoptosis.ConclusionsThe study identified potential genes and integrated functional modules associated with the hematopoietic and endothelial differentiation of human ESCs.