Drp1 is dispensable for mitochondria biogenesis in induction to pluripotency but required for differentiation of embryonic stem cells.
Drp1 is dispensable for mitochondria biogenesis in induction to pluripotency but required for differentiation of embryonic stem cells.
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DOI：
10.1089/scd.2014.0059
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发表时间：
2014-06
影响因子：
4
通讯作者：
Lei Wang;Xiaoying Ye;Qiang Zhao;Zhongcheng Zhou;Jiameng Dan;Yushan Zhu;Quan Chen;Lin Liu
中科院分区：
文献类型：
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作者：
Lei Wang;Xiaoying Ye;Qiang Zhao;Zhongcheng Zhou;Jiameng Dan;Yushan Zhu;Quan Chen;Lin Liu
具有高氧化磷酸化的成熟线粒体在从体细胞诱导多能干细胞（iPS）期间经历分裂和融合以及形态发生以变成未成熟线粒体。动力蛋白相关蛋白1（Drp1）参与体细胞线粒体分裂和生物合成。我们测试了Drp1在诱导和维持多能性中的作用。我们发现，Drp1带移位发生在胚胎干细胞（ESC）和诱导成纤维细胞的iPS细胞（iPSC），与线粒体形态发生。然而，通过shRNA敲低Drp1并不消除线粒体形态发生和从成纤维细胞诱导iPSC。此外，敲除Drp1既不影响正常线粒体膜电位所示的线粒体分裂和功能，也不影响ESC的增殖和多能性。尽管如此，Drp1敲低对ESC的终末分化产生负面影响，特别是在体外和体内的神经发生谱系中，与中期分化期间Oct4和Nanog的延迟减少一致。我们的数据表明，Drp1在干细胞增殖中对线粒体生物发生并不重要，但它可能是通过下调多能性相关基因Nanog和Oct4来实现神经发生所必需的。ESC分化模型可用于模拟Drp1在神经元发育和疾病中的作用。
Mature mitochondria with high oxidative phosphorylation undergo fission and fusion and morphogenesis to become immature mitochondria during induced pluripotent stem (iPS) induction from somatic cells. Dynamin-related protein 1 (Drp1) is involved in mitochondria fission and biogenesis in somatic cells. We tested the role of Drp1 in the induction and maintenance of pluripotency. We show that Drp1 band shift occurs in embryonic stem cells (ESCs) and iPS cells (iPSCs) induced from fibroblasts, in association with mitochondrial morphogenesis. However, knockdown of Drp1 by shRNA does not abrogate mitochondria morphogenesis and induction of iPSCs from fibroblasts. Also, knockdown of Drp1 affects neither mitochondria fission and function as shown by normal mitochondrial membrane potential, nor proliferation and pluripotency of ESCs. Nonetheless, Drp1 knockdown negatively influences terminal differentiation of ESCs, particularly in the lineage of neurogenesis in vitro and in vivo, coincident with delayed reduction of Oct4 and Nanog during mid-differentiation. Our data suggest that Drp1 is not critical for mitochondria biogenesis in stem cell proliferation but it is required for neurogenesis likely by downregulation of pluripotency-associated genes Nanog and Oct4. ESC differentiation model could be used to model role of Drp1 in neuron development and diseases.