Miyagi-Shiohira Chika, Saitoh Issei, Watanabe Masami, Noguchi Hirofumi
Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata 951-8514, Japan.
J Clin Med. 2021 Jan 25;10(3):454. doi: 10.3390/jcm10030454.
We previously reported that transient overexpression of reprogramming factors can be used to generate induced pluripotent stem (iPS) cells, induced tissue-specific stem (iTS) cells, and fibroblast-like (iF) cells from pancreatic tissue. iF cells have tumorigenic ability and behave similarly to pancreatic cancer cells. In this study, we analyzed gene expression in iF cells and iTS-P cells (iTS cells from pancreatic tissue) via microarray analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression levels of the Mybl2 and Lyn genes, which are reported to be oncogenes, were significantly higher in iF cells than in iTS-P cells. The expression level of Nestin, which is expressed in not only pancreatic progenitor cells but also pancreatic ductal adenocarcinomas, was also higher in iF cells than in iTS-P cells. Itgb6 and Fgf13, which are involved in the pathogenesis of diseases such as cancer, exhibited higher expression levels in iF cells than in iTS-P cells. Unexpectedly, the expression levels of genes related to epithelial-mesenchymal transition (EMT), except Bmp4, were lower in iF cells than in iTS-P cells. These data suggest that the Mybl2, Lyn, Nestin, Itgb6, and Fgf13 genes could be important biomarkers to distinguish iTS-P cells from iF cells.
我们之前报道过，重编程因子的瞬时过表达可用于从胰腺组织中生成诱导多能干细胞（iPS细胞）、诱导组织特异性干细胞（iTS细胞）和成纤维样细胞（iF细胞）。iF细胞具有致瘤能力，其行为与胰腺癌细胞相似。在本研究中，我们通过微阵列分析和定量逆转录-聚合酶链反应（qRT-PCR）分析了iF细胞和iTS-P细胞（来自胰腺组织的iTS细胞）中的基因表达。据报道为癌基因的Mybl2和Lyn基因的表达水平在iF细胞中显著高于iTS-P细胞。巢蛋白（Nestin）不仅在胰腺祖细胞中表达，在胰腺导管腺癌中也有表达，其在iF细胞中的表达水平同样高于iTS-P细胞。参与癌症等疾病发病机制的整合素β6（Itgb6）和成纤维细胞生长因子13（Fgf13）在iF细胞中的表达水平高于iTS-P细胞。出乎意料的是，除骨形态发生蛋白4（Bmp4）外，与上皮-间质转化（EMT）相关的基因在iF细胞中的表达水平低于iTS-P细胞。这些数据表明，Mybl2、Lyn、Nestin、Itgb6和Fgf13基因可能是区分iTS-P细胞和iF细胞的重要生物标志物。
