Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.
BMC Genet. 2013 Apr 30;14:32. doi: 10.1186/1471-2156-14-32.
hiPSCs are generated through epigenetic reprogramming of somatic tissue. Genomic imprinting is an epigenetic phenomenon through which monoallelic gene expression is regulated in a parent-of-origin-specific manner. Reprogramming relies on the successful erasure of marks of differentiation while maintaining those required for genomic imprinting. Loss of imprinting (LOI), which occurs in many types of malignant tumors, would hinder the clinical application of hiPSCs.
We examined the imprinting status, expression levels and DNA methylation status of eight imprinted genes in five independently generated hiPSCs. We found a low frequency of LOI in some lines. Where LOI was identified in an early passage cell line, we found that this was maintained through subsequent passages of the cells. Just as normal imprints are maintained in long-term culture, this work suggests that abnormal imprints are also stable in culture.
Analysis of genomic imprints in hiPSCs is a necessary safety step in regenerative medicine, with relevance both to the differentiation potential of these stem cells and also their potential tumorigenic properties.
hiPSCs 是通过体细胞的表观遗传重编程产生的。基因组印记是一种表观遗传现象，通过这种现象，单等位基因的表达以亲本来源特异性的方式受到调控。重编程依赖于成功擦除分化标记，同时保持基因组印记所需的标记。印迹丢失（LOI）发生在许多类型的恶性肿瘤中，这将阻碍 hiPSCs 的临床应用。
我们检查了五个独立生成的 hiPSCs 中八个印记基因的印迹状态、表达水平和 DNA 甲基化状态。我们发现一些系中 LOI 的频率较低。在早期传代细胞系中鉴定出 LOI 时，我们发现随着细胞的后续传代，这种情况得以维持。就像正常印记在长期培养中得以维持一样，这项工作表明异常印记在培养中也很稳定。
对 hiPSCs 中基因组印记的分析是再生医学中必要的安全步骤，这与这些干细胞的分化潜能以及它们潜在的致瘤特性都有关。
