Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.
Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Stem Cell Res. 2023 Sep;71:103171. doi: 10.1016/j.scr.2023.103171. Epub 2023 Jul 23.
SIX2-positive urine derived renal progenitor cells were isolated from a male and female alpha1-antitrypsin deficiency (AATD) patients both harboring the homozygous PiZZ genotype. The cells were reprogrammed to generate two integration-free induced pluripotent stem cell (iPSC) lines by transfecting episomal-based plasmids expressing OCT4, SOX2, NANOG, c-MYC, KLF4 and LIN28. Pluripotency was confirmed by immunocytochemistry for associated markers and embryoid body-based differentiation into the three germ layers. The iPSC lines carried the parental PiZZ genotype. Comparative transcriptome analyses with human embryonic stem cell line H9 revealed a Pearson correlation of 0.945 for ISRM-AATD-iPSC-1 and 0.939 for ISRM-AATD-iPSC-2 respectively.
从一名男性和一名女性α1-抗胰蛋白酶缺乏症（AATD）患者的尿液中分离出 SIX2 阳性肾祖细胞，这两名患者均携带纯合 PiZZ 基因型。通过转染表达 OCT4、SOX2、NANOG、c-MYC、KLF4 和 LIN28 的基于附加体的质粒，将细胞重编程为产生两个无整合的诱导多能干细胞（iPSC）系。通过免疫细胞化学鉴定相关标志物和类胚体分化为三个胚层来确认多能性。iPSC 系携带亲本 PiZZ 基因型。与人类胚胎干细胞系 H9 的比较转录组分析显示，ISRM-AATD-iPSC-1 的皮尔逊相关系数为 0.945，ISRM-AATD-iPSC-2 的皮尔逊相关系数为 0.939。
