Department of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan.
Manufacturing Technology Association of Biologics, Kobe, Japan.
PLoS One. 2022 Mar 31;17(3):e0266061. doi: 10.1371/journal.pone.0266061. eCollection 2022.
Immortalized kidney cell lines are widely used in basic and applied research such as cell permeability tests and drug screening. Although many cell lines have been established from kidney tissues, the immortalization process has not been clarified in these cell lines. In this study, we analyzed the phenotypic changes that occurred during the immortalization of kidney cells derived from Chinese hamster tissue in terms of karyotype and gene expression profiles. In the newly established cell line, designated as CHK-Q, gene expression profiles at each stage of the immortalization process and during the adaptation to serum-free conditions were analyzed by DNA microarray. Renal stem cell markers CD24 and CD133 were expressed in CHK-Q cells, suggesting that CHK-Q cells were transformed from renal stem cells. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to identify the pathways of upregulated and downregulated genes revealed that the immortalization of CHK-Q cells was associated with increased fluctuations in the expression of specific proto-oncogenes. Karyotype analysis of spontaneously immortalized CHK-Q cells indicated that CHK-Q chromosomes had a typical modal number of 23 but possessed slight chromosomal abnormalities. In this study, we investigated the mechanism of cell environmental adaptation by analyzing gene expression behavior during the immortalization process and serum-free adaptation. CHK-Q cells are applicable to the fields of biotechnology and biomedical science by utilizing their characteristics as kidney-derived cells.
永生化肾细胞系广泛应用于基础和应用研究,如细胞通透性试验和药物筛选。虽然已经从肾脏组织中建立了许多细胞系,但这些细胞系中的永生化过程尚未阐明。在这项研究中,我们从中国仓鼠组织中分析了肾细胞永生化过程中发生的表型变化,包括染色体组型和基因表达谱。在新建立的细胞系 CHK-Q 中,通过 DNA 微阵列分析了永生化过程各个阶段以及适应无血清条件下的基因表达谱。CHK-Q 细胞表达肾干细胞标志物 CD24 和 CD133,表明 CHK-Q 细胞是由肾干细胞转化而来的。京都基因与基因组百科全书(KEGG)途径富集分析鉴定上调和下调基因的途径表明,CHK-Q 细胞的永生化与特定原癌基因表达的波动增加有关。自发永生化 CHK-Q 细胞的染色体组型分析表明,CHK-Q 染色体具有典型的 23 条模式数,但存在轻微的染色体异常。在这项研究中,我们通过分析永生化过程和无血清适应过程中的基因表达行为,研究了细胞环境适应的机制。利用 CHK-Q 细胞作为肾源性细胞的特性,它们可应用于生物技术和生物医学科学领域。