biostudies-literatureLiao YCNCI NIH HHSNIGMS NIH HHS100491https://www.ebi.ac.uk/biostudies/studies/S-EPMC9944986biostudies-literatureUnknown22(2)Conventional proteomic approaches measure the averaged signal from mixed cell populations or bulk tissues, leading to the dilution of signals arising from subpopulations of cells that might serve as important biomarkers. Recent developments in bottom-up proteomics have enabled spatial mapping of cellular heterogeneity in tissue microenvironments. However, bottom-up proteomics cannot unambiguously define and quantify proteoforms, which are intact (i.e., functional) forms of proteins capturing genetic variations, alternatively spliced transcripts and posttranslational modifications. Herein, we described a spatially resolved top-down proteomics (TDP) platform for proteoform identification and quantitation directly from tissue sections. The spatial TDP platform consisted of a nanodroplet proceMolecular & cellular proteomics : MCPSpatially Resolved Top-Down Proteomics of Tissue Sections Based on a Microfluidic Nanodroplet Sample Preparation Platform.PMC9944986UG3 CA256959P41 GM108569UH3 CA256959Zhou MZhu YVelickovic DSontag RLFulcher JMPasa-Tolic LLiao YCBramer LMDegnan DJWilliams SMMoore RJZemaitis KJVelickovic MfalseSpatially Resolved Top-Down Proteomics of Tissue Sections Based on a Microfluidic Nanodroplet Sample Preparation Platform.Conventional proteomic approaches measure the averaged signal from mixed cell populations or bulk tissues, leading to the dilution of signals arising from subpopulations of cells that might serve as important biomarkers. Recent developments in bottom-up proteomics have enabled spatial mapping of cellular heterogeneity in tissue microenvironments. However, bottom-up proteomics cannot unambiguously define and quantify proteoforms, which are intact (i.e., functional) forms of proteins capturing genetic variations, alternatively spliced transcripts and posttranslational modifications. Herein, we described a spatially resolved top-down proteomics (TDP) platform for proteoform identification and quantitation directly from tissue sections. The spatial TDP platform consisted of a nanodroplet proce2023-01-01T00:00:00Z2023 Feb2026-03-31T11:00:07.566Z2025-04-04T19:00:29.578ZS-EPMC99449863660380610.1016/j.mcpro.2022.100491