Single-cell nanobiopsy enables multigenerational longitudinal transcriptomics of cancer cells

Marcuccio, Fabio, Chau, Chalmers C., Tanner, Georgette, Elpidorou, Marilena, Finetti, Martina A., Ajaib, Shoaib, Taylor, Morag, Lascelles, Carolina, Carr, Ian, Macaulay, Iain, Stead, Lucy F. and Actis, Paolo (2024) Single-cell nanobiopsy enables multigenerational longitudinal transcriptomics of cancer cells. Science Advances, 10 (10). ISSN 2375-2548

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Abstract

Single-cell RNA sequencing has revolutionized our understanding of cellular heterogeneity, but routine methods require cell lysis and fail to probe the dynamic trajectories responsible for cellular state transitions, which can only be inferred. Here, we present a nanobiopsy platform that enables the injection of exogenous molecules and multigenerational longitudinal cytoplasmic sampling from a single cell and its progeny. The technique is based on scanning ion conductance microscopy (SICM) and, as a proof of concept, was applied to longitudinally profile the transcriptome of single glioblastoma (GBM) brain tumor cells in vitro over 72 hours. The GBM cells were biopsied before and after exposure to chemotherapy and radiotherapy, and our results suggest that treatment either induces or selects for more transcriptionally stable cells. We envision the nanobiopsy will contribute to transforming standard single-cell transcriptomics from a static analysis into a dynamic assay.

Item Type: Article
Additional Information: Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. The ion current data, optical micrographs, raw sequencing data and the code used for data analysis are openly available from the University of Leeds data repository at: https://doi.org/10.5518/1464 and from https://github.com/GliomaGenomics/GBM_NB. Funding Information: This work was supported by The Brain Tumour Charity (TBTC) grant number GN-000482 (to L.F.S. and P.A.), U.K. Research and Innovation (UKRI) grant number MR/T020504/1 (to L.F.S.), and European Commission H2020 grant number 812398 (to P.A.).
Uncontrolled Keywords: general,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School: Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 24 Oct 2024 14:30
Last Modified: 01 Nov 2024 12:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/97183
DOI: 10.1126/sciadv.adl0515

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