Expression data from Werner syndrome iPSCs

Werner syndrome (WS) is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. We used microarrays to examine whether global gene expression profile of WS iPSCs is similar to that of normal iPSCs and human ESCs, as well as premature senescence phenotype is suppressed by reprogramming. Total RNAs extracted from WS fibroblasts, WS iPSCs, normal iPSCs, and human ESCs were hybridized onto Human Genome U133 Plus 2.0 Arrays to compare global gene expression profile of WS iPSCs with normal human pluripotent stem cells, as well as the parental fibroblasts.

沃纳综合征（Werner syndrome, WS）是一类以染色体不稳定及癌症易感性为特征的早老性疾病。WRN基因突变是该病的致病根源，可引发端粒功能异常，进而导致机体衰老加速。本研究探讨了长期培养对沃纳综合征诱导多能干细胞（induced pluripotent stem cells, iPSCs）的影响：该细胞系在长达2年的培养周期中获得并维持了无限增殖的自我更新能力。经长期培养后，WS iPSCs仍保持稳定的未分化状态与分化潜能；尽管存在WRN基因缺陷，WS细胞中提前出现的衰老相关基因上调现象在WS iPSCs中被完全抑制。本研究采用基因芯片技术，旨在探究两个科学问题：一是WS iPSCs的全局基因表达谱是否与正常iPSCs及人类胚胎干细胞（human embryonic stem cells, ESCs）相似；二是重编程是否可抑制早衰表型。研究人员从沃纳综合征成纤维细胞、WS iPSCs、正常iPSCs及人类ESCs中提取总RNA，将其与人类基因组U133 Plus 2.0芯片进行杂交，以此对比WS iPSCs与正常人类多能干细胞及其亲本成纤维细胞的全局基因表达谱。