TY - JOUR
T1 - Differential Influence of Sample Sex and Neuronal Maturation on mRNA and Protein Transport in Induced Human Neurons
AU - Ding, Baojin
AU - Akter, Masuma
AU - Zhang, Chun Li
N1 - Funding Information:
We thank Mr. Jacob Stagray for constructive criticism of the manuscript. Funding. This work was supported by the Friends of the Alzheimer?s Disease Center (ADC) and NIH ADC grant (NIH/NIA P30-12300-21 to BD), the DoD PRMRP grant (W81XWH2010186 to BD), the Welch Foundation (I-1724), the Decherd Foundation, the Pape Adams Foundation, Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, and NIH Grants (NS099073, NS092616, and NS088095 to C-LZ, and R21NS112910 to BD).
Funding Information:
This work was supported by the Friends of the Alzheimer’s Disease Center (ADC) and NIH ADC grant (NIH/NIA P30-12300-21 to BD), the DoD PRMRP grant (W81XWH2010186 to BD), the Welch Foundation (I-1724), the Decherd Foundation, the Pape Adams Foundation, Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, and NIH Grants (NS099073, NS092616, and NS088095 to C-LZ, and R21NS112910 to BD).
Publisher Copyright:
© Copyright © 2020 Ding, Akter and Zhang.
PY - 2020/4/3
Y1 - 2020/4/3
N2 - 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.
AB - 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.
KW - fluorescence in situ hybridization (FISH)
KW - nuclear mRNA export
KW - nucleocytoplasmic transport
KW - protein nuclear transport
KW - reprogrammed human neurons
KW - sex as a biological variable (SABV)
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U2 - 10.3389/fnmol.2020.00046
DO - 10.3389/fnmol.2020.00046
M3 - Article
C2 - 32317929
AN - SCOPUS:85083504909
SN - 1662-5099
VL - 13
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 46
ER -