Single-cell nanobiopsy enables multigenerational longitudinal transcriptomics of cancer cells.

in Science advances by Fabio Marcuccio, Chalmers C Chau, Georgette Tanner, Marilena Elpidorou, Martina A Finetti, Shoaib Ajaib, Morag Taylor, Carolina Lascelles, Ian Carr, Iain Macaulay, Lucy F Stead, Paolo Actis

TLDR

  • The nanobiopsy platform is a new way to study cells that allows us to see how they change over time. The study used the platform to look at brain tumor cells and found that treatment either made them more stable or selected for more stable cells. This could help us understand how to better treat brain tumors.

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.

Overview

  • The study presents 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 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 the results suggest that treatment either induces or selects for more transcriptionally stable cells. The study aims to transform standard single-cell transcriptomics from a static analysis into a dynamic assay.

Comparative Analysis & Findings

  • The study compared the outcomes observed under different experimental conditions or interventions, specifically the effects of chemotherapy and radiotherapy on GBM cells. The results showed that treatment either induced or selected for more transcriptionally stable cells. This finding suggests that the nanobiopsy platform can provide valuable insights into the dynamic trajectories responsible for cellular state transitions and the effects of different interventions on these trajectories.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they suggest that the nanobiopsy platform can transform standard single-cell transcriptomics into a dynamic assay. This assay could provide valuable insights into the effects of different interventions on cellular state transitions and the selection of more transcriptionally stable cells. Future research directions could include the application of the nanobiopsy platform to other cell types and the investigation of the effects of other interventions on cellular state transitions.
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