Non-random segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in daughter cells

Ioannis Segos, Jens Van Eeckhoven, Simon Berger, Nikhil Mishra, Eric Lambie, Barbara Conradt
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Abstract

The non-random segregation of organelles has been proposed to be an intrinsic mechanism that contributes to cell fate divergence during asymmetric cell division; however, in vivo evidence is sparse. Using super-resolution microscopy, we analysed the segregation of organelles during the division of the neuroblast QL.p in C. elegans larvae. QL.p divides to generate a daughter that survives, QL.pa, and a daughter that dies, QL.pp. We found that mitochondria segregate unequally by density and morphology and that this is dependent on mitochondrial fission and fusion. Furthermore, we found that mitochondrial density in QL.pp correlates with the time it takes QL.pp to die. We propose that low mitochondrial density in QL.pp promotes the cell death fate and ensures that QL.pp dies in a highly reproducible and timely manner. Our results provide the first in vivo evidence that the non-random segregation of mitochondria can contribute to cell fate divergence during asymmetric cell division.
不对称细胞分裂过程中线粒体的非随机分离有助于子细胞的细胞命运分化
细胞器的非随机分离被认为是不对称细胞分裂过程中导致细胞命运分化的内在机制;然而,体内证据却很稀少。我们利用超分辨率显微镜分析了优雅小鼠幼虫神经母细胞 QL.p 分裂过程中的细胞器分离。QL.p分裂产生一个存活的子细胞QL.pa和一个死亡的子细胞QL.pp。我们发现,线粒体在密度和形态上的分离是不平等的,这取决于线粒体的裂变和融合。此外,我们还发现 QL.pp 中的线粒体密度与 QL.pp 的死亡时间相关。我们认为,QL.pp 中线粒体密度低会促进细胞死亡命运,并确保 QL.pp 以高度可重现和及时的方式死亡。我们的研究结果首次提供了体内证据,证明线粒体的非随机分离有助于不对称细胞分裂过程中的细胞命运分化。
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