Vera Elsa, Bosco Nazario, Studer Lorenz
Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave., New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave., New York, NY 10065, USA.
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, Box 159, New York, NY 10065, USA.
Cell Rep. 2016 Oct 18;17(4):1184-1192. doi: 10.1016/j.celrep.2016.09.062.
Modeling late-onset disorders such as Parkinson's disease (PD) using iPSC technology remains a challenge, as current differentiation protocols yield cells with the properties of fetal-stage cells. Here, we tested whether it is possible to accelerate aging in vitro to trigger late-onset disease phenotypes in an iPSC model of PD. In order to manipulate a factor that is involved in natural aging as well as in premature aging syndromes, we used telomere shortening as an age-inducing tool. We show that shortened telomeres result in age-associated as well as potentially disease-associated phenotypes in human pluripotent stem cell (hPSC)-derived midbrain dopamine (mDA) neurons. Our approach provides proof of concept for the further validation of telomere shortening as an induced-aging tool for late-onset-disease modeling.
利用诱导多能干细胞（iPSC）技术对帕金森病（PD）等迟发性疾病进行建模仍然是一项挑战，因为目前的分化方案产生的细胞具有胎儿期细胞的特性。在此，我们测试了是否有可能在体外加速衰老，以在PD的iPSC模型中触发迟发性疾病表型。为了操控一个与自然衰老以及早衰综合征都相关的因素，我们使用端粒缩短作为一种诱导衰老的工具。我们发现，端粒缩短会在人多能干细胞（hPSC）衍生的中脑多巴胺（mDA）神经元中导致与年龄相关以及潜在的与疾病相关的表型。我们的方法为进一步验证端粒缩短作为迟发性疾病建模的诱导衰老工具提供了概念验证。
