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Integrated Single-Cell Proteomic and Morphometric Analysis Reveals Heterogeneous Drug-Resistant Subpopulations
Qian-Xi Fan1, Yi-Rong Jiang1, Jian-Bo Chen1
1Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.
Abstract:
Investigating the heterogeneous responses of individual cancer cells to chemotherapeutic drugs is crucial for deciphering the mechanisms of cancer drug resistance. In recent years, single-cell proteomics has demonstrated its significant capability in exploring drug response in cancer cells. Meanwhile, there are increasing reports suggesting that the cellular morphology is potentially associated with drug resistance. However, integrating the single-cell proteomic results with morphological information remains challenging. Here, we present a morphology-aware single-cell proteomic analysis (Morp-SCP) platform to precisely capture cells of interest with real-time and high-resolution imaging, and to conduct deep proteomic analysis at the single-cell level, providing multidimensional information on the target single cells. The Morp-SCP platform was applied for exploring the time-dependent proteomic alterations of human nonsmall cell lung cancer cells (A549) upon cisplatin exposure. Subpopulations of drug-resistant A549 cells were identified, which exhibited distinct proteomic and morphological patterns when resisting cell death induced by cisplatin exposure. By revealing the proteomics-morphology relationship, the Morp-SCP platform offers an effective strategy to provide insights into the heterogeneity of drug resistance at the single-cell level.
Insights
Understanding cancer drug resistance requires studying individual cell responses. A new platform integrates single-cell proteomics and cell morphology to reveal drug-resistant cancer cell subpopulations and their unique patterns.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Investigating heterogeneous cancer cell responses to chemotherapy is vital for understanding drug resistance mechanisms.
- Single-cell proteomics offers powerful insights into cellular drug responses.
- Linking cellular morphology to drug resistance is an emerging area, but integrating these data remains challenging.
Purpose of the Study:
- To develop and present a novel morphology-aware single-cell proteomic analysis (Morp-SCP) platform.
- To integrate high-resolution imaging with deep proteomic analysis at the single-cell level.
- To provide multidimensional data for understanding single-cell heterogeneity in drug response.
Main Methods:
- Development of the Morp-SCP platform for real-time, high-resolution cell imaging and capture.
- Application of Morp-SCP to analyze time-dependent proteomic alterations in human nonsmall cell lung cancer cells (A549) exposed to cisplatin.
- Deep proteomic analysis of single cells identified through imaging.
Main Results:
- Identification of distinct subpopulations of cisplatin-resistant A549 cells.
- Characterization of unique proteomic and morphological patterns in drug-resistant subpopulations.
- Demonstration of a correlation between proteomics and morphology in single cancer cells resisting chemotherapy.
Conclusions:
- The Morp-SCP platform effectively integrates proteomic and morphological data for single-cell analysis.
- This approach reveals insights into the heterogeneity of cancer drug resistance at the single-cell level.
- The findings highlight the potential of morphology-aware single-cell proteomics in cancer research and drug development.
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