Department of Oral Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima-City, Hiroshima, 734-8553, Japan.
Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University, Kochi, Japan.
In Vitro Cell Dev Biol Anim. 2023 Jun;59(6):395-400. doi: 10.1007/s11626-023-00778-y. Epub 2023 Jul 17.
It is known that a nevoid basal cell carcinoma syndrome (NBCCS) is characterized by a combination of developmental abnormalities and a predisposition to form various tumors. Although it is possible to create disease models via gene editing, there are significant potential problems with this approach such as off-target mutations and differences in SNPs. On the other hand, since disease families share common SNPs, research using iPSCs derived from both patients and healthy siblings of the same disease family is very important. Thus, establishment of induced pluripotent stem cells derived from patients and healthy siblings of the same NBCCS family will be of great importance to study the etiology of this disease and to develop therapeutics. In this study, we generated hiPSCs using peripheral blood mononuclear cells derived from the patients and healthy siblings of familial NBCCS with the novel mutation in PTCH1_c.3298_3299insAAG in the feeder- and serum-free culture conditions using SeVdp. In addition, disease-specific hiPSCs such as those expressing the PTCH1_c.3298_3299insAAG mutation could be powerful tools for revealing the genotype-phenotype relationship and pathogenicity of NBCCS.
已知结节性基底细胞癌综合征（NBCCS）的特征是发育异常和易形成各种肿瘤的倾向相结合。虽然通过基因编辑可以创建疾病模型，但这种方法存在着明显的潜在问题，如脱靶突变和单核苷酸多态性（SNP）的差异。另一方面，由于疾病家族共享共同的 SNP，因此使用来自同一疾病家族的患者和健康兄弟姐妹的 iPSC 进行研究非常重要。因此，建立源自同一 NBCCS 家族的患者和健康兄弟姐妹的诱导多能干细胞，对于研究该疾病的病因和开发治疗方法将具有重要意义。在这项研究中，我们使用新型突变 PTCH1_c.3298_3299insAAG 在无饲养细胞和无血清培养条件下，从携带该突变的 NBCCS 家系患者和健康兄弟姐妹的外周血单核细胞中生成 hiPSC。此外，表达 PTCH1_c.3298_3299insAAG 突变的疾病特异性 hiPSC 可以成为揭示 NBCCS 的基因型-表型关系和致病性的有力工具。
