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Facile sample preparation for quantitative single-cell proteomics

ABSTRACT: Large numbers of cells are generally required for quantitative global proteome profiling due to the significant 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, such as circulating tumor cells (CTCs) and early metastatic cells. Herein we report a facile mass spectrometry (MS)-based single-cell proteomics method that capitalizes on a MS-compatible nonionic surfactant, n-Dodecyl-β-D-maltoside, for greatly reducing the surface adsorption losses by ~20-fold for effective single-tube processing of single cells, thus significantly improving detection sensitivity for single-cell proteomic analysis. With standard MS platforms, the method allows for the first time precise, label-free, reliable quantification of hundreds of proteins from single human cells in a simple, convenient manner. When applied to a patient CTC-derived xenograft (PCDX) model, the method can reveal distinct protein signatures between primary tumor cells and early metastases to the lungs at the single-cell resolution. The approach paves the way for routine, precise quantitative single-cell proteomic analysis.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Tujin Shi

PROVIDER: PXD017075 | JPOST Repository | Mon Jun 07 00:00:00 BST 2021

REPOSITORIES: jPOST

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