Establishment of maturity-onset diabetes of the young-induced pluripotent stem cells from a Japanese patient.
Establishment of maturity-onset diabetes of the young-induced pluripotent stem cells from a Japanese patient.
复制标题
DOI：
10.1111/jdi.12334
复制
发表时间：
2015-09
影响因子：
3.2
通讯作者：
Okochi H
中科院分区：
文献类型：
--
作者：
Yabe SG;Iwasaki N;Yasuda K;Hamazaki TS;Konno M;Fukuda S;Takeda F;Kasuga M;Okochi H
青壮年型糖尿病（MODY）是一种杂合单基因糖尿病；目前已经确定了超过13种疾病基因。然而，MODY的发病机制尚不完全清楚，因为患者的胰腺β细胞是不可接近的。因此，我们尝试建立MODY患者源性诱导多能干细胞（MODY- ips）细胞，通过诱导胰腺β细胞来研究MODY的致病机制。我们从日本MODY5 （R177X）患者身上建立了MODY5- ips细胞，并证实了MODY5- ips细胞具有多能干细胞的特征。在MODY5-iPS细胞向胰腺β-细胞分化的过程中，我们检测了疾病基因HNF1B信使核糖核酸。我们发现R177X突变体转录本的数量比野生的少得多，但在培养基中加入环己亚胺后转录本数量增加。这些结果表明，在胰腺β细胞发育阶段，这些R177X突变体信使核糖核酸在MODY-iPS细胞中被无义介导的信使核糖核酸衰变破坏。
Maturity-onset diabetes of the young (MODY) is a heterozygous monogenic diabetes; more than 13 disease genes have been identified. However, the pathogenesis of MODY is not fully understood, because the pancreatic β-cells of the patients are inaccessable. Therefore, we attempted to establish MODY patient-derived induced pluripotent stem cells (MODY-iPS) cells to investigate the pathogenic mechanism of MODY by inducing pancreatic β-cells. We established MODY5-iPS cells from a Japanese patient with MODY5 (R177X), and confirmed that MODY5-iPS cells possessed the characteristics of pluripotent stem cells. In the course of differentiation from MODY5-iPS cells into pancreatic β-cells, we examined the disease gene, HNF1B messenger ribonucleic acid. We found that the amount of R177X mutant transcripts was much less than that of wild ones, but they increased after adding cycloheximide to the medium. These results suggest that these R177X mutant messenger ribonucleic acids are disrupted by nonsense-mediated messenger ribonucleic acid decay in MODY-iPS cells during the developmental stages of pancreatic β-cells.