Bang Jin Seok, Choi Na Young, Lee Minseong, Ko Kisung, Park Yo Seph, Ko Kinarm
Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea.
Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.
Int J Stem Cells. 2019 Nov 30;12(3):430-439. doi: 10.15283/ijsc19067.
Several recent studies have claimed that cancer cells can be reprogrammed into induced pluripotent stem cells (iPSCs). However, in most cases, cancer cells seem to be resistant to cellular reprogramming. Furthermore, the underlying mechanisms of limited reprogramming in cancer cells are largely unknown. Here, we identified the candidate barrier genes and their target genes at the early stage of reprogramming for investigating cancer reprogramming.
We tried induction of pluripotency in normal human fibroblasts (BJ) and both human benign (MCF10A) and malignant (MCF7) breast cancer cell lines using a classical retroviral reprogramming method. We conducted RNA-sequencing analysis to compare the transcriptome of the three cell lines at early stage of reprogramming.
We could generate iPSCs from BJ, whereas we were unable to obtain iPSCs from cancer cell lines. To address the underlying mechanism of limited reprogramming in cancer cells, we identified 29 the candidate barrier genes based on RNA-sequencing data. In addition, we found 40 their target genes using Cytoscape software.
Our data suggest that these genes might one of the roadblock for cancer cell reprogramming. Furthermore, we provide new insights into application of iPSCs technology in cancer cell field for therapeutic purposes.
最近的几项研究声称癌细胞可被重编程为诱导多能干细胞（iPSC）。然而，在大多数情况下，癌细胞似乎对细胞重编程具有抗性。此外，癌细胞中重编程受限的潜在机制在很大程度上尚不清楚。在此，我们在重编程早期鉴定了候选屏障基因及其靶基因，以研究癌症重编程。
我们使用经典的逆转录病毒重编程方法，尝试在正常人成纤维细胞（BJ）以及人良性（MCF10A）和恶性（MCF7）乳腺癌细胞系中诱导多能性。我们进行了RNA测序分析，以比较重编程早期这三种细胞系的转录组。
我们能够从BJ细胞系生成iPSC，而无法从癌细胞系中获得iPSC。为了探究癌细胞重编程受限的潜在机制，我们基于RNA测序数据鉴定了29个候选屏障基因。此外，我们使用Cytoscape软件找到了40个它们的靶基因。
我们的数据表明这些基因可能是癌细胞重编程的障碍之一。此外，我们为iPSC技术在癌细胞领域用于治疗目的的应用提供了新的见解。
