Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell.
10.1016/j.apsb.2025.02.039
- Author:
Zhun LIN
1
;
Siping LIANG
2
;
Zhe PU
1
;
Zhengyu ZOU
2
;
Luxuan HE
1
;
Christopher J LYON
3
;
Yuanqing ZHANG
1
;
Tony Y HU
3
;
Minhao WU
2
Author Information
1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
3. Center of Cellular and Molecular Diagnosis, Tulane University School of Medicine, New Orleans, LA 70112, USA.
- Publication Type:Journal Article
- Keywords:
Autocrine secretion;
Cancer stem cells;
Growth factor;
Microfluidic;
Phenotypic plasticity;
Phenotypic transition;
Single-cell analysis;
Tumor heterogeneity
- From:
Acta Pharmaceutica Sinica B
2025;15(5):2723-2735
- CountryChina
- Language:English
-
Abstract:
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.
