Enhanced Telomere Rejuvenation in Pluripotent Cells Reprogrammed via Nuclear Transfer Relative to Induced Pluripotent Stem Cells

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• 作者：Rongrong Le ; Zhaohui Kou ; Yonghua Jiang ; Ming Li ; Bo Huang ; Wenqiang Liu ; Hui Li ; Xiaochen Kou ; Wanzhong He ; Karl聽Lenhard Rudolph ; Zhenyu Ju ; Shaorong Gao
• 刊名：Cell Stem Cell
• 出版年：2 January, 2014
• 年：2014
• 卷：14
• 期：1
• 页码：27-39
• 全文大小：4019 K

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Summary

Although somatic cell nuclear transfer (SCNT) and induction of pluripotency (to form iPSCs) are both recognized reprogramming methods, there has been relatively little comparative analysis of the resulting pluripotent cells. Here, we examine the capacity of these two reprogramming approaches to rejuvenate telomeres using late-generation telomerase-deficient (Terc^{鈭?鈭?/sup>) mice that exhibit telomere dysfunction and premature aging. We found that embryonic stem cells established from Terc鈭?鈭?/sup> SCNT embryos (Terc鈭?鈭?/sup> ntESCs) have greater differentiation potential and self-renewal capacity than Terc鈭?鈭?/sup> iPSCs. Remarkably, SCNT results in extensive telomere lengthening in cloned embryos and improved telomere capping function in the established Terc鈭?鈭?/sup> ntESCs. In addition, mitochondrial function is severely impaired in Terc鈭?鈭?/sup> iPSCs and their differentiated derivatives but significantly improved in Terc鈭?鈭?/sup> ntESCs. Thus, our results suggest that SCNT-mediated reprogramming mitigates telomere dysfunction and mitochondrial defects to a greater extent than iPSC-based reprogramming. Understanding the basis of this differential could help optimize reprogramming strategies.}