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Tsai, Chia-Feng; Zhang, Pengfei; Scholten, David; Martin, Kendall; Wang, Yi-Ting; Zhao, Rui; Chrisler, William B; Patel, Dhwani B; Dou, Maowei; Jia, Yuzhi; Reduzzi, Carolina; Liu, Xia; Moore, Ronald J; Burnum-Johnson, Kristin E; Lin, Miao-Hsia; Hsu, Chuan-Chih; Jacobs, Jon M; Kagan, Jacob; Srivastava, Sudhir; Rodland, Karin D; Steven Wiley, H; Qian, Wei-Jun; Smith, Richard D; Zhu, Ying; Cristofanilli, Massimo; Liu, Tao; Liu, Huiping; Shi, Tujin
Communications biology, 03/2021, Letnik: 4, Številka: 1Journal Article
Large numbers of cells are generally required for quantitative global proteome profiling due to surface adsorption losses associated with sample processing. Such bulk measurement obscures important cell-to-cell variability (cell heterogeneity) and makes proteomic profiling impossible for rare cell populations (e.g., circulating tumor cells (CTCs)). Here we report a surfactant-assisted one-pot sample preparation coupled with mass spectrometry (MS) method termed SOP-MS for label-free global single-cell proteomics. SOP-MS capitalizes on the combination of a MS-compatible nonionic surfactant, n-Dodecyl-β-D-maltoside, and hydrophobic surface-based low-bind tubes or multi-well plates for 'all-in-one' one-pot sample preparation. This 'all-in-one' method including elimination of all sample transfer steps maximally reduces surface adsorption losses for effective processing of single cells, thus improving detection sensitivity for single-cell proteomics. This method allows convenient label-free quantification of hundreds of proteins from single human cells and ~1200 proteins from small tissue sections (close to ~20 cells). When applied to a patient CTC-derived xenograft (PCDX) model at the single-cell resolution, SOP-MS can reveal distinct protein signatures between primary tumor cells and early metastatic lung cells, which are related to the selection pressure of anti-tumor immunity during breast cancer metastasis. The approach paves the way for routine, precise, quantitative single-cell proteomics.
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