Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells.
Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells.
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DOI：
10.1016/j.dib.2015.10.023
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发表时间：
2015-12
期刊：
影响因子：
1.2
通讯作者：
Arumugaswami V
中科院分区：
文献类型：
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作者：
Ignatius Irudayam J;Contreras D;Spurka L;Ren S;Kanagavel V;Ramaiah A;Annamalai A;French SW;Klein AS;Funari V;Arumugaswami V
在人多能干细胞（PSC）分化为肝细胞的过程中，分析了与炎症相关的基因的表达。通过RNA测序分析获得分化的内胚层（第5天）、成肝细胞（第15天）和肝细胞样细胞（第21天）的信使RNA转录谱。当与内胚层细胞（一种未成熟细胞类型）相比时，肝细胞（第15天和第21天）具有显著更高的急性期蛋白基因表达，包括补体因子、凝血因子、血清淀粉样蛋白A和丝氨酸蛋白酶抑制剂。此外，肝期细胞表达促炎细胞因子IL 18和IL 32以及细胞因子受体IL 18 R1、IL 1 R1、IL 1 RAP、IL 2 RG、IL 6 R、IL 6ST和IL 10 RB。这些细胞还产生CCL 14、CCL 15和CXCL- 1、2、3、16和17趋化因子。内胚层细胞比肝细胞具有更高水平的趋化因子受体CXCR 4和CXCR 7。Sirtuin家族基因参与衰老、炎症和代谢，在内胚层和肝期细胞中受到不同的调控。肿瘤坏死因子（TNF）家族的配体和受体以及下游信号传导因子TRAF 2、TRAF 4、FADD、NFKB 1和NFKBIB在肝分化期间差异表达。
Expression of genes associated with inflammation was analyzed during differentiation of human pluripotent stem cells (PSCs) to hepatic cells. Messenger RNA transcript profiles of differentiated endoderm (day 5), hepatoblast (day 15) and hepatocyte-like cells (day 21) were obtained by RNA sequencing analysis. When compared to endoderm cells an immature cell type, the hepatic cells (days 15 and 21) had significantly higher expression of acute phase protein genes including complement factors, coagulation factors, serum amyloid A and serpins. Furthermore, hepatic phase of cells expressed proinflammatory cytokines IL18 and IL32 as well as cytokine receptors IL18R1, IL1R1, IL1RAP, IL2RG, IL6R, IL6ST and IL10RB. These cells also produced CCL14, CCL15, and CXCL- 1, 2, 3, 16 and 17 chemokines. Endoderm cells had higher levels of chemokine receptors, CXCR4 and CXCR7, than that of hepatic cells. Sirtuin family of genes involved in aging, inflammation and metabolism were differentially regulated in endoderm and hepatic phase cells. Ligands and receptors of the tumor necrosis factor (TNF) family as well as downstream signaling factors TRAF2, TRAF4, FADD, NFKB1 and NFKBIB were differentially expressed during hepatic differentiation.