Henke Marie-Thérèse, Zink Annika, Diecke Sebastian, Prigione Alessandro, Schuelke Markus
Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), NeuroCure Cluster of Excellence, Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Neuropediatrics, Berlin, Germany.
Medical Faculty, Heinrich Heine University, Düsseldorf, Department of General Pediatrics, Neonatology and Pediatric Cardiology, Düsseldorf, Germany.
Stem Cell Res. 2023 Mar;67:103030. doi: 10.1016/j.scr.2023.103030. Epub 2023 Jan 17.
We generated two pairs of mother-child iPSCs lines for Maternally Inherited Leigh Syndrome (MILS) carrying the m.8993 T > G and m.9176 T > G mutations in the MT-ATP6 gene. We delivered reprogramming factors OCT4, SOX2, KLF4, and c-MYC via Sendai virus. All iPSCs lines had a normal karyotype, expressed pluripotency markers, and differentiated into the three germ layers. Both patient-iPSCs retained the same degrees of heteroplasmy as their source fibroblasts (>97.0 %). In maternal iPSCs, the heteroplasmy remained 0.0 % in the case of the m.8993 T > G mutation and dropped from 55.0 % to 1.0 % in the case of m.9176 T > G mutation.
我们为患有母系遗传 Leigh 综合征（MILS）的患者构建了两对母子诱导多能干细胞系，这些患者的线粒体 ATP 合酶 6 亚基（MT-ATP6）基因携带 m.8993 T>G 和 m.9176 T>G 突变。我们通过仙台病毒递送重编程因子 OCT4、SOX2、KLF4 和 c-MYC。所有诱导多能干细胞系均具有正常的核型，表达多能性标志物，并分化为三个胚层。两个患者诱导多能干细胞系与其来源的成纤维细胞保持相同程度的异质性（>97.0%）。在母源诱导多能干细胞中，对于 m.8993 T>G 突变，异质性保持为 0.0%；对于 m.9176 T>G 突变，异质性从 55.0%降至 1.0%。
