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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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383525001340 |
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| author | Zhun Lin Siping Liang Zhe Pu Zhengyu Zou Luxuan He Christopher J. Lyon Yuanqing Zhang Tony Y. Hu Minhao Wu |
| author_facet | Zhun Lin Siping Liang Zhe Pu Zhengyu Zou Luxuan He Christopher J. Lyon Yuanqing Zhang Tony Y. Hu Minhao Wu |
| author_sort | Zhun Lin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-979eecab72ca4bd4ba8360e3e33db8a6 |
| institution | DOAJ |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-979eecab72ca4bd4ba8360e3e33db8a62025-08-20T03:09:57ZengElsevierActa Pharmaceutica Sinica B2211-38352025-05-011552723273510.1016/j.apsb.2025.02.039Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cellZhun Lin0Siping Liang1Zhe Pu2Zhengyu Zou3Luxuan He4Christopher J. Lyon5Yuanqing Zhang6Tony Y. Hu7Minhao Wu8School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaZhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaZhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaCenter of Cellular and Molecular Diagnosis, Tulane University School of Medicine, New Orleans, LA 70112, USASchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Corresponding authors.Center of Cellular and Molecular Diagnosis, Tulane University School of Medicine, New Orleans, LA 70112, USA; Corresponding authors.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2211383525001340Single-cell analysisMicrofluidicCancer stem cellsPhenotypic transitionPhenotypic plasticityTumor heterogeneity |
| spellingShingle | Zhun Lin Siping Liang Zhe Pu Zhengyu Zou Luxuan He Christopher J. Lyon Yuanqing Zhang Tony Y. Hu Minhao Wu Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell Acta Pharmaceutica Sinica B Single-cell analysis Microfluidic Cancer stem cells Phenotypic transition Phenotypic plasticity Tumor heterogeneity |
| title | Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell |
| title_full | Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell |
| title_fullStr | Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell |
| title_full_unstemmed | Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell |
| title_short | Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell |
| title_sort | phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell |
| topic | Single-cell analysis Microfluidic Cancer stem cells Phenotypic transition Phenotypic plasticity Tumor heterogeneity |
| url | http://www.sciencedirect.com/science/article/pii/S2211383525001340 |
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