Mitochondrial rejuvenation after induced pluripotency.
Mitochondrial rejuvenation after induced pluripotency.
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DOI：
10.1371/journal.pone.0014095
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发表时间：
2010-11-23
期刊：
影响因子：
3.7
通讯作者：
Cibelli JB
中科院分区：
文献类型：
--
作者：
Suhr ST;Chang EA;Tjong J;Alcasid N;Perkins GA;Goissis MD;Ellisman MH;Perez GI;Cibelli JB
随着早期胚胎的干细胞成熟并分化成所有组织，线粒体补体经历了显着的功能改善。线粒体活性较低，以最大限度地减少植入前发育过程中DNA损伤性活性氧的产生，并在植入和分化后增加，以满足更高的代谢需求。最近有报道称，当被称为诱导多能干细胞（IPSC）的干细胞类型在体外再分化数周时，线粒体补体逐渐重新获得接近输入成纤维细胞的特性，这表明尽管观察到IPSC转化"重置"了细胞老化的一些参数，如端粒长度，它可能对其它受年龄影响的细胞系统如IPSC衍生细胞中的线粒体几乎没有影响。我们已经检查了两个成纤维细胞系，相应的IPSC，和使用生物化学方法和电子显微镜从IPSC再衍生的成纤维细胞中的线粒体的性质，并发现与输入成纤维细胞相比，再衍生的成纤维细胞的线粒体补体的质量和功能有了显着的改善。这一观察结果可能源于我们实验设计的两个方面：1）所用的输入细胞系具有晚期细胞年龄并且含有低效的线粒体补体，以及2）使用广泛的分化方案产生再衍生的成纤维细胞，所述广泛的分化方案可以更接近地模拟在发育中的哺乳动物中发现的生长和成熟程度。这些结果-再加上我们实验室早期的数据-表明IPSC转换不仅重置了“生物钟”，而且还可以恢复衍生细胞的能量能力。
As stem cells of the early embryo mature and differentiate into all tissues, the mitochondrial complement undergoes dramatic functional improvement. Mitochondrial activity is low to minimize generation of DNA-damaging reactive oxygen species during pre-implantation development and increases following implantation and differentiation to meet higher metabolic demands. It has recently been reported that when the stem cell type known as induced pluripotent stem cells (IPSCs) are re-differentiated for several weeks in vitro, the mitochondrial complement progressively re-acquires properties approximating input fibroblasts, suggesting that despite the observation that IPSC conversion “resets” some parameters of cellular aging such as telomere length, it may have little impact on other age-affected cellular systems such as mitochondria in IPSC-derived cells. We have examined the properties of mitochondria in two fibroblast lines, corresponding IPSCs, and fibroblasts re-derived from IPSCs using biochemical methods and electron microscopy, and found a dramatic improvement in the quality and function of the mitochondrial complement of the re-derived fibroblasts compared to input fibroblasts. This observation likely stems from two aspects of our experimental design: 1) that the input cell lines used were of advanced cellular age and contained an inefficient mitochondrial complement, and 2) the re-derived fibroblasts were produced using an extensive differentiation regimen that may more closely mimic the degree of growth and maturation found in a developing mammal. These results — coupled with earlier data from our laboratory — suggest that IPSC conversion not only resets the “biological clock”, but can also rejuvenate the energetic capacity of derived cells.
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