Differential Influence of Sample Sex and Neuronal Maturation on mRNA and Protein Transport in Induced Human Neurons
Differential Influence of Sample Sex and Neuronal Maturation on mRNA and Protein Transport in Induced Human Neurons
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样本性别和神经元成熟度对诱导人类神经元中 mRNA 和蛋白质转运的差异影响
DOI：
10.3389/fnmol.2020.00046
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发表时间：
2020-04-03
影响因子：
4.8
通讯作者：
Zhang, Chun-Li
中科院分区：
文献类型：
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作者：
Ding, Baojin;Akter, Masuma;Zhang, Chun-Li
核质转运（NCT）是真核细胞中一种受严格调控的跨核膜转运（NE）过程，对维持细胞内环境的稳定至关重要。它的失调会导致衰老和神经退化。由于它们具有与衰老相关的特征，因此来自人成纤维细胞的直接重编程神经元在理解NCT方面是非常宝贵的。然而，目前尚不清楚NCT活性是否受到神经元成熟和样本性别的影响[美国国立卫生研究院（NIH）政策强调的关键生物学变量]。在这里，我们研究了在单细胞水平的NCT活性，通过测量mRNA的亚细胞分布和蛋白质转运直接诱导的运动神经元（diMN）从成人成纤维细胞。结果表明，mRNA的亚细胞分布，而不是蛋白质运输的神经元成熟阶段的影响，而这两个运输过程不受样本的性别。这项研究还提供了定量方法和优化的条件，用于测量mRNA或蛋白质货物的NCT，建立了一个强大的方式，为未来的功能检查的NCT活性在直接诱导的神经元从患病的人类患者。
Nucleocytoplasmic transport (NCT) across thenuclear envelope (NE) is tightly regulated in eukaryotic cells and iscritical for maintaining cellular homeostasis. Its dysregulationleads to aging and neurodegeneration. Because they maintainaging-associated hallmarks, directly reprogrammed neurons from human fibroblasts are invaluable in understanding NCT. However, it is not clear whether NCT activity is influenced by neuronal maturation and sample sex [a key biological variable emphasized by the National Institutes of Health (NIH) policy]. We examined here NCT activity at the single-cell level by measuring mRNA subcellular distribution and protein transport in directly induced motor neurons (diMNs) from adult human fibroblasts. The results show that mRNA subcellular distribution but not protein transport is affected by neuronal maturation stages, whereas both transport processes are not influenced by the sample sex. This study also provides quantitative methods and optimized conditions for measuring NCTs of mRNAs or protein cargoes, establishing a robust way for future functional examinations of NCT activity in directly induced neurons from diseased human patients.