Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell

Single-cell analysis of phenotypic plasticity could improve the development of more effective therapeutics. Still, the development of tools to measure single-cell heterogeneity has lagged due to difficulties in manipulating and culturing single cells. Here, we describe a single-cell culture and phen...

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Bibliographic Details
Main Authors: Zhun Lin, Siping Liang, Zhe Pu, Zhengyu Zou, Luxuan He, Christopher J. Lyon, Yuanqing Zhang, Tony Y. Hu, Minhao Wu
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Acta Pharmaceutica Sinica B
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211383525001340
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Summary:Single-cell analysis of phenotypic plasticity could improve the development of more effective therapeutics. Still, the development of tools to measure single-cell heterogeneity has lagged due to difficulties in manipulating and culturing single cells. Here, we describe a single-cell culture and phenotyping platform that employs a starburst microfluidic network and automatic liquid handling system to capture single cells for long-term culture and multi-dimensional analysis and quantify their clonal properties via their surface biomarker and secreted cytokine/growth factor profiles. Studies performed on this platform found that cells derived from single-cell cultures maintained phenotypic equilibria similar to their parental populations. Single-cell cultures exposed to chemotherapeutic drugs stochastically disrupted this balance to favor stem-like cells. They had enhanced expression of mRNAs and secreted factors associated with cell signaling, survival, and differentiation. This single-cell analysis approach can be extended to analyze more complex phenotypes and screen responses to therapeutic targets.
ISSN:2211-3835