Analysis of differentially expressed genes among human hair follicle-derived iPSCs, induced hepatocyte-like cells, and primary hepatocytes.
Analysis of differentially expressed genes among human hair follicle-derived iPSCs, induced hepatocyte-like cells, and primary hepatocytes.
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人毛囊来源的iPSC、诱导肝细胞样细胞和原代肝细胞差异表达基因分析
DOI：
10.1186/s13287-018-0940-z
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发表时间：
2018-08-09
影响因子：
7.5
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Xu Z;He X;Shi X;Xia Y;Liu X;Wu H;Li P;Zhang H;Yin W;Du X;Li L;Li Y
诱导人多能干细胞（hiPSCs）向肝细胞分化，为终末期肝病的细胞治疗提供新的干细胞来源，具有重要的临床意义。hiPSC、诱导的肝细胞样细胞（HLC）和原代人肝细胞（PHH）的差异基因表达分析为优化诱导方案和探索分化机制提供了有价值的信息。通过模拟发育中的肝脏环境体外诱导人毛囊来源的iPSC（hHF-iPSC）19天。免疫荧光染色检测特异性蛋白表达;检测高碘酸希夫碱、吲哚菁绿色和低密度脂蛋白，鉴定HLCs在储存和代谢中的功能。基于转录组学数据，采用Gene Ontology、京都基因百科全书和基因组通路、FunRich和网络分析等方法对hHF-iPSCs、HLC和PHH的差异基因表达谱进行分析。HLCs能够表达白蛋白（ALB）、甲胎蛋白、CYP 3A 4和CYP 7A 1，并表现出成熟的肝细胞功能，如糖原合成和储存。补体和凝血级联和代谢途径在HLC/PHH的下调列表中排名第一，而细胞周期在HLC/PHH的上调列表中排名第一。在蛋白质-蛋白质相互作用网络中，根据度排序，TOP 2A、CDK 1等是HLC/PHH中重要的上调差异表达基因（DEG），而ALB、ACACB等是HLC/PHH中主要的下调DEG;模块分析表明，CDCA 8、AURKB和AURKA是HLC/PHH中上调最多的DEG。我们通过转录组阵列数据展示了hHF-iPSCs、HLCs和PHH之间基因表达的差异，为优化诱导提供了新思路。本文的在线版本（10.1186/s13287-018-0940-z）包含补充材料，可供授权用户使用。
Differentiation of human induced pluripotent stem cells (hiPSCs) into hepatocytes has important clinical significance in providing a new stem cell source for cell therapy of terminal liver disease. The differential gene expression analysis of hiPSCs, induced hepatocyte-like cells (HLCs), and primary human hepatocytes (PHHs) provides valuable information for optimization of an induction scheme and exploration of differentiation mechanisms. Human hair follicle-derived iPSCs (hHF-iPSCs) were induced in vitro by mimicking the environment of a developing liver for 19 days. Expression of specific proteins was determined by immunofluorescence staining; the function of HLCs in storage and metabolism was identified by detecting periodic acid–Schiff, indocyanine green, and low-density lipoprotein. Based on the transcriptomics data, the differential gene expression profiles of hHF-iPSCs, HLCs, and PHHs were analyzed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, FunRich, and network analysis methods. HLCs were able to express albumin (ALB), alpha-fetoprotein, CYP3A4, and CYP7A1, and exhibited matured liver cell functions such as glycogen synthesis and storage. Complement and coagulation cascades and metabolic pathways ranked top in the downregulated list of HLCs/PHHs, while the cell cycle ranked top in the upregulated list of HLCs/PHHs. In the protein–protein interaction network, according to the degree rankings, TOP2A, CDK1, etc. were the important upregulated differentially expressed genes (DEGs), while ALB, ACACB, etc. were the major downregulated DEGs in HLCs/PHHs; the module analysis indicated that CDCA8, AURKB, and AURKA were the top upregulated DEGs in HLCs/PHHs. We presented the differences in gene expression among hHF-iPSCs, HLCs, and PHHs through transcriptome array data and provided new ideas for the optimization of induction. The online version of this article (10.1186/s13287-018-0940-z) contains supplementary material, which is available to authorized users.
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影响因子：
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