Spatial and temporal single-cell profiling of RNA compartmentalization in neurons with nanotweezers
Author(s)
Type
Journal Article
Abstract
Emerging techniques for mapping mRNAs within the subcellular compartments of live cells hold great promise for advancing our understanding of the spatial distribution of transcripts and enabling the study of single-cell dynamics in health and disease. This is particularly critical for polarized cells, such as neurons, where mRNA compartmentalization is essential for regulating gene expression, and defects in these localization mechanisms are linked to numerous neurological disorders. However, many subcellular analysis techniques require a compromise between subcellular precision, live-cell measurements, and nondestructive access to single cells in their native microenvironment. To overcome these challenges, we employ a single-cell technology that we have recently developed, the nanotweezer, which features a nanoscale footprint (∼100 nm), avoids cytoplasmic fluid aspiration, and enables rapid RNA isolation from living cells with minimal invasiveness. Using this tool, we investigate single-cell mRNA compartmentalization in the soma and dendrites of hippocampal neurons at different stages of neuronal development. By combining precise targeting with sequential sampling, we track changes in mRNA abundance at dendritic spine regions of the same neuron, both before and after stimulation. This minimally invasive approach enables time-resolved, subcellular gene expression profiling of the same single cell. This could provide critical insights into polarized cells and advance our understanding of biological processes and complex diseases.
Date Issued
2025-05-20
Date Acceptance
2025-04-24
Citation
ACS Nano, 2025, 19 (19), pp.18522-18533
ISSN
1936-0851
Publisher
American Chemical Society
Start Page
18522
End Page
18533
Journal / Book Title
ACS Nano
Volume
19
Issue
19
Copyright Statement
© 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
License URL
Identifier
10.1021/acsnano.5c02056
Subjects
single-cell
nanotweezer
nanobiopsy
neuron
RNA
synaptic plasticity
Publication Status
Published
Date Publish Online
2025-05-06