Differential Influence of Sample Sex and Neuronal Maturation on mRNA and Protein Transport in Induced Human Neurons

Baojin Ding, Masuma Akter, Chun Li Zhang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number46
JournalFrontiers in Molecular Neuroscience
Volume13
DOIs
StatePublished - Apr 3 2020

Keywords

  • fluorescence in situ hybridization (FISH)
  • nuclear mRNA export
  • nucleocytoplasmic transport
  • protein nuclear transport
  • reprogrammed human neurons
  • sex as a biological variable (SABV)

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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