Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation
Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation
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DOI：
10.7554/elife.38904
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发表时间：
2019-01-14
期刊：
影响因子：
7.7
通讯作者：
Carey, Lucas B.
中科院分区：
文献类型：
--
作者：
Dhar, Riddhiman;Missarova, Alsu M.;Carey, Lucas B.
突变往往会在不同的人身上产生不同的结果，即使这些人在基因上是相同的，并共享共同的环境。此外，单个微生物和哺乳动物细胞的增殖率、应激耐受性和抗药性可能有很大差异，这对感染和癌症的治疗具有重要意义。为了研究细胞间增殖差异的原因，我们使用了高通量自动显微镜分析方法来量化酵母中>；1500基因缺失的影响。影响线粒体的突变在它们的结果中尤其不同。在突变型和野生型细胞中，线粒体膜电位--但不是数量--在单个细胞之间有很大的差异，并预测了细胞之间在增殖、突变结果、应激耐受性和对临床使用的抗真菌药物的耐药性方面的差异。这些结果表明，细胞器状态的细胞间变异在单细胞表型变异中起着重要作用。
Mutations frequently have outcomes that differ across individuals, even when these individuals are genetically identical and share a common environment. Moreover, individual microbial and mammalian cells can vary substantially in their proliferation rates, stress tolerance, and drug resistance, with important implications for the treatment of infections and cancer. To investigate the causes of cell-to-cell variation in proliferation, we used a high-throughput automated microscopy assay to quantify the impact of deleting >1500 genes in yeast. Mutations affecting mitochondria were particularly variable in their outcome. In both mutant and wild-type cells mitochondrial membrane potential - but not amount - varied substantially across individual cells and predicted cell-to-cell variation in proliferation, mutation outcome, stress tolerance, and resistance to a clinically used anti-fungal drug. These results suggest an important role for cell-to-cell variation in the state of an organelle in single cell phenotypic variation.