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首页> 外文期刊>Cell metabolism >Mitochondrial Dynamics Is Critical for the Full Pluripotency and Embryonic Developmental Potential of Pluripotent Stem Cells
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Mitochondrial Dynamics Is Critical for the Full Pluripotency and Embryonic Developmental Potential of Pluripotent Stem Cells

机译:线粒体动态对于多能干细胞的全多能性和胚胎发育潜力至关重要

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摘要

While the pluripotency of stem cells is known to determine the fate of embryonic development, the mechanisms underlying the acquisition and maintenance of full pluripotency largely remain elusive. Here, we show that the balance between mitochondrial fission and fusion is critical for the full pluripotency of stem cells. By analyzing induced pluripotent stem cells with differential developmental potential, we found that excess mitochondrial fission is associated with an impaired embryonic developmental potential. We further uncover that the disruption of mitochondrial dynamics impairs the differentiation and embryonic development of pluripotent stem cells; most notably, pluripotent stem cells that display excess mitochondrial fission fail to produce live-born offspring by tetraploid complementation. Mechanistically, excess mitochondrial fission increases cytosolic Ca2+ entry and CaMKII activity, leading to ubiquitin-mediated proteasomal degradation of beta-Catenin protein. Our results reveal a previously unappreciated fundamental role for mitochondrial dynamics in determining the full pluripotency and embryonic developmental potential of pluripotent stem cells.
机译:虽然已知干细胞的多能性来确定胚胎发育的命运,但是依赖于全多能性的潜在的机制在很大程度上难以难以捉摸。在这里,我们表明线粒体裂变与融合之间的平衡对于干细胞的全多能性至关重要。通过分析具有鉴别发育潜力的诱导多能干细胞,我们发现多余的线粒体裂变与胚胎发育潜力受损有关。我们进一步揭示了线粒体动力学的破坏损害了多能干细胞的分化和胚胎发育;最值得注意的是,显示过量线粒体裂变的多能干细胞不能通过四倍体互补产生活生生的后代。机械地,过量的线粒体裂变增加了细胞溶质Ca2 +进入和Camkii活性,导致泛素介导的β-连环蛋白蛋白蛋白的蛋白质降解。我们的结果揭示了在测定多能干细胞的全多能性和胚胎发育潜力时,对线粒体动力学进行了以前未被珍视的基本作用。

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  • 来源
    《Cell metabolism》 |2019年第4期|共18页
  • 作者单位

    South China Univ Technol Guangzhou Peoples Hosp 1 Sch Med Guangzhou 510006 Guangdong Peoples R;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Anhui Med Univ Sch Med Dept Pathol Hefei 230022 Anhui Peoples R China;

    Univ Sci &

    Technol China Sch Life Sci CAS Key Lab Innate Immun &

    Chron Dis Div Mol Med Hefei;

    Univ Sci &

    Technol China Sch Life Sci CAS Key Lab Innate Immun &

    Chron Dis Div Mol Med Hefei;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Anhui Med Univ Sch Med Dept Pathol Hefei 230022 Anhui Peoples R China;

    South China Univ Technol Guangzhou Peoples Hosp 1 Sch Med Guangzhou 510006 Guangdong Peoples R;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Natl Ctr Biomed Anal Inst Basic Med Sci Beijing 100853 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Univ Sci &

    Technol China Sch Life Sci CAS Key Lab Innate Immun &

    Chron Dis Div Mol Med Hefei;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    South China Univ Technol Guangzhou Peoples Hosp 1 Sch Med Guangzhou 510006 Guangdong Peoples R;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

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