論文 - 詳細
| RRC ID | 85957 |
|---|---|
| 著者 | Muneer G, Gebreyesus ST, Chen CS, Lee TT, Yu F, Lin CA, Hsieh MS, Nesvizhskii AI, Ho CC, Yu SL, Tu HL, Chen YJ. |
| タイトル | Mapping Nanoscale-To-Single-Cell Phosphoproteomic Landscape by Chip-DIA. |
| ジャーナル | Adv Sci (Weinh) |
| Abstract |
Protein phosphorylation plays a crucial role in regulating disease phenotypes and serves as a key target for drug development. Mapping nanoscale-to-single-cell samples can unravel the heterogeneity of cellular signaling events. However, it remains a formidable analytical challenge due to the low detectability, abundance, and stoichiometry of phosphorylation sites. Here, we present a Chip-DIA strategy, integrating a microfluidic-based phosphoproteomic chip (iPhosChip) with data-independent acquisition mass spectrometry (DIA-MS) for ultrasensitive nanoscale-to-single-cell phosphoproteomic profiling. The iPhosChip operates as an all-in-one station that accommodates both quantifiable cell capture/imaging and the entire phosphoproteomic workflow in a highly streamlined and multiplexed manner. Coupled with a sample size-comparable library-based DIA-MS strategy, Chip-DIA achieved ultra-high sensitivity, detecting 1076±158 to 15869±1898 phosphopeptides from 10±0 to 1013±4 cells, and revealed the first single-cell phosphoproteomic landscape comprising druggable sites and basal phosphorylation-mediated networks in lung cancer. Notably, the sensitivity and coverage enabled the illumination of heterogeneous cytoskeleton remodeling and cytokeratin signatures in patient-derived cells resistant to third-generation EGFR therapy, stratifying mixed-lineage adenocarcinoma-squamous cell carcinoma subtypes, and identifying alternative targeted therapy for late-stage patients. With flexibility in module design and functionalization, Chip-DIA can be adapted to other PTM-omics to explore dysregulated PTM landscapes, thereby guiding therapeutic strategies toward precision oncology. |
| 巻・号 | 12(1) |
| ページ | e2402421 |
| 公開日 | 2025-1-1 |
| DOI | 10.1002/advs.202402421 |
| PMID | 39401432 |
| PMC | PMC11714195 |
| MeSH | Cell Line, Tumor Humans Lung Neoplasms / metabolism Mass Spectrometry / methods Phosphoproteins / metabolism Phosphorylation Proteomics* / methods Single-Cell Analysis* / methods |
| IF | 15.84 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-9(RCB4455) |