In Vitro Cellular & Developmental Biology - Animal ( IF 2.1 ) Pub Date : 2020-11-02 , DOI: 10.1007/s11626-020-00515-9 Atsuko Hamada 1 , Eri Akagi 1 , Fumitaka Obayashi 1 , Sachiko Yamasaki 1 , Koichi Koizumi 2 , Manami Ohtaka 3, 4 , Ken Nishimura 5 , Mahito Nakanishi 3, 4 , Shigeaki Toratani 2 , Tetsuji Okamoto 2
Noonan syndrome is an autosomal dominant developmental disorder. Although it is relatively common, and its phenotypical variability is well documented, its pathophysiology is not fully understood. Previously, with the aim of revealing the pathogenesis of genetic disorders, we reported the induction of cleidocranial dysplasia-specific human-induced pluripotent stem cells (hiPSCs) from patient’s dental pulp cells (DPCs) under serum-free, feeder-free, and integration-free conditions. Notably, these cells showed potential for application to genetic disorder disease models. Furthermore, using similar procedures, we reported the induction of hiPSCs derived from peripheral blood mononuclear cells (PBMCs) of healthy volunteers. These methods are beneficial, because they are carried out without invasive and painful biopsies. Using those procedures, we reprogrammed DPCs and PBMCs that were derived from a patient with Noonan syndrome (NS) to establish NS-specific hiPSCs (NS-DPC-hiPSCs and NS-PBMC-hiPSCs, respectively). The induction efficiency of NS-hiPSCs was higher than that of WT-hiPSCs. We hypothesize that this was caused by high NANOG expression. Here, we describe the experimental results and findings related to NS-hiPSCs. This is the first report on the establishment of NS-hiPSCs and their disease modeling.
中文翻译:
在无血清、无饲养层和无整合条件下诱导 Noonan 综合征特异性人诱导多能干细胞
努南综合征是一种常染色体显性遗传发育障碍。尽管它相对常见,并且其表型变异性有据可查,但其病理生理学尚未完全了解。以前,为了揭示遗传疾病的发病机制,我们报道了在无血清、无饲养层和整合下从患者牙髓细胞 (DPC) 中诱导颅骨发育不良特异性人诱导多能干细胞 (hiPSC) 的过程。 - 免费条件。值得注意的是,这些细胞显示出应用于遗传疾病模型的潜力。此外,使用类似的程序,我们报告了来自健康志愿者的外周血单核细胞 (PBMC) 的 hiPSC 的诱导。这些方法是有益的,因为它们在没有侵入性和痛苦的活检的情况下进行。使用这些程序,我们重新编程了源自 Noonan 综合征 (NS) 患者的 DPC 和 PBMC,以建立 NS 特异性 hiPSC(分别为 NS-DPC-hiPSC 和 NS-PBMC-hiPSC)。NS-hiPSCs的诱导效率高于WT-hiPSCs。我们假设这是由高NANOG表达式。在这里,我们描述了与 NS-hiPSC 相关的实验结果和发现。这是关于建立 NS-hiPSC 及其疾病模型的第一份报告。