Mitochondrial dynamics regulates Drosophila intestinal stem cell differentiation.
Mitochondrial dynamics regulates Drosophila intestinal stem cell differentiation.
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DOI：
10.1038/s41420-018-0083-0
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发表时间：
2018
影响因子：
7
通讯作者：
Hartenstein V
中科院分区：
文献类型：
--
作者：
Deng H;Takashima S;Paul M;Guo M;Hartenstein V
干/祖细胞的分化与线粒体质量和复杂性的显著增加相关。线粒体动力学，包括融合和分裂过程，在诱导多能细胞（iPSC）中体细胞重编程和多能性维持中起着重要作用。然而，线粒体动力学在体内干/祖细胞分化过程中的作用仍然难以捉摸。我们发现果蝇肠道干细胞的分化过程中伴随着线粒体的不断融合。线粒体融合缺陷（opa 1 RNAi）ISC含有较少的线粒体膜电位、减少的ATP和增加的ROS水平。令人惊讶的是，抑制融合也导致祖细胞分化失败。细胞没有开启分化标志物的表达，而是继续显示祖细胞的特征。同时，增殖或凋亡不受影响。分化缺陷可以通过同时抑制线粒体分裂分子Drp 1来挽救。此外，ROS清除剂还通过下调JNK活性部分挽救opa 1 RNAi相关的分化缺陷。我们认为线粒体融合在控制干细胞命运的发育开关中起着关键作用。
Differentiation of stem/progenitor cells is associated with a substantial increase in mitochondrial mass and complexity. Mitochondrial dynamics, including the processes of fusion and fission, plays an important role for somatic cell reprogramming and pluripotency maintenance in induced pluripotent cells (iPSCs). However, the role of mitochondrial dynamics during stem/progenitor cell differentiation in vivo remains elusive. Here we found differentiation of Drosophila intestinal stem cell is accompanied with continuous mitochondrial fusion. Mitochondrial fusion defective(opa1RNAi) ISCs contain less mitochondrial membrane potential, reduced ATP, and increased ROS level. Surprisingly, suppressing fusion also resulted in the failure of progenitor cells to differentiate. Cells did not switch on the expression of differentiation markers, and instead continued to show characteristics of progenitor cells. Meanwhile, proliferation or apoptosis was unaffected. The differentiation defect could be rescued by concomitant inhibition of Drp1, a mitochondrial fission molecule. Moreover, ROS scavenger also partially rescues opa1RNAi-associated differentiation defects via down-regulating JNK activity. We propose that mitochondrial fusion plays a pivotal role in controlling the developmental switch of stem cell fate.
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通讯作者：
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