Single-cell nanobiopsy enables multigenerational longitudinal transcriptomics of cancer cells
Single-cell nanobiopsy enables multigenerational longitudinal transcriptomics of cancer cells
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DOI：
10.1126/sciadv.adl0515
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发表时间：
2024-03-06
期刊：
影响因子：
13.6
通讯作者：
Actis，Paolo
中科院分区：
文献类型：
--
作者：
Marcuccio，Fabio;Chau，Chalmers C.;Actis，Paolo
单细胞RNA测序彻底改变了我们对细胞异质性的理解，但常规方法需要细胞裂解，无法探测细胞状态转变的动态轨迹，这只能推断。在这里，我们提出了一个纳米活检平台，可以注射外源分子，并从单个细胞及其后代中进行多代纵向细胞质取样。该技术基于扫描离子电导显微镜（SICM），并作为概念验证，应用于体外培养超过72小时的单个胶质母细胞瘤（GBM）脑肿瘤细胞的纵向转录组分析。在化疗和放疗前后对GBM细胞进行活检，结果表明治疗诱导或选择了转录更稳定的细胞。我们设想纳米活检将有助于将标准单细胞转录组学从静态分析转变为动态分析。
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.