Kong Chiou Mee, Arjunan Subramanian, Gan Shu Uin, Biswas Arijit, Bongso Ariff, Fong Chui-Yee
Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, 1E Kent Ridge Rd, Singapore 119228, Singapore.
Department of Surgery, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, 1E Kent Ridge Rd, Singapore 119228, Singapore.
Stem Cell Res. 2020 Jun 26;47:101880. doi: 10.1016/j.scr.2020.101880.
Gestational diabetes mellitus (GDM) has been strongly associated with an increased risk of type 2 diabetes mellitus (T2DM) in later child and adulthood. The human umbilical cord and its contents are of fetal origin and represent the fetus genetically and physiologically. Since it is not possible to obtain tissues from the fetus and newborn to investigate the association between GDM and later T2DM, we reprogrammed the stem cells from the Wharton's jelly of umbilical cords (hWJSCs) of GDM and non-GDM mothers into induced pluripotent stem cells (iPSCs) and then differentiated the iPSCs into insulin-producing cells (IPCs) to provide pancreatic tissues that represent the fetus of GDM and normal mothers. These tissues are an attractive model to study the effects of glucose on the fetus. Interestingly, GDM-iPSCs had a decreased potential towards differentiation into IPCs. IPCs differentiated from GDM-iPSCs also had lower total insulin content and a lower capacity for insulin secretion to glucose stimulation compared to their normal-iPSC counterparts. This abnormal pathogenesis in GDM-iPSCs pancreatic differentiation recapitulates the pathology that may be observed in the infants of the diabetic mother (IDM) and while indicating adaptive mechanisms for fetal survival, may lead to the development of T2DM later in life. (199 words).
妊娠期糖尿病（GDM）与儿童期及成年后期患2型糖尿病（T2DM）的风险增加密切相关。人脐带及其所含物质源自胎儿，在遗传和生理上代表胎儿。由于无法从胎儿和新生儿获取组织来研究GDM与后期T2DM之间的关联，我们将GDM和非GDM母亲脐带华通氏胶中的干细胞（hWJSCs）重编程为诱导多能干细胞（iPSCs），然后将iPSCs分化为胰岛素生成细胞（IPCs），以提供代表GDM母亲和正常母亲胎儿的胰腺组织。这些组织是研究葡萄糖对胎儿影响的有吸引力的模型。有趣的是，GDM-iPSCs分化为IPCs的潜能降低。与正常iPSC分化而来的IPCs相比，GDM-iPSCs分化而来的IPCs总胰岛素含量更低，对葡萄糖刺激的胰岛素分泌能力也更低。GDM-iPSCs胰腺分化中的这种异常发病机制概括了糖尿病母亲婴儿（IDM）中可能观察到的病理情况，在表明胎儿生存的适应性机制的同时，可能导致日后患T2DM。 （199字）
