ArticleProceedings of the National Academy of Sciences of the United States of America2023
High sensitivity top-down proteomics captures single muscle cell heterogeneity in large proteoforms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Review
- Proteomic Profiling of Myofiber Repair Annexins and Their Role in Duchenne Muscular Dystrophy.Proteomics · 2026Review
- Top-Down versus Bottom-Up Proteomics in Highly Sensitive LC-MS-Based Profiling of Limited Samples.Analytical chemistry · 2026Article
- Subcellular localization as a driver of protein function.Nature reviews. Molecular cell biology · 2026Review
- Proteoform profiling of endogenous single cells from rat hippocampus at scale.Nature biotechnology · 2026Article
- Capturing Cardiomyocyte Cell-to-Cell Heterogeneity via Shotgun Single Cell Top-Down Proteomics.bioRxiv : the preprint server for biology · 2026Article
- Top-Down Proteomics of Skinned Human Muscle Fibers Reveals Proteoform-Resolved Fiber-to-Fiber Variability.Journal of mass spectrometry : JMS · 2026Article
- Advances in Mass Spectrometry Instrumentation and Methodology for Analysis of Alternative Protein Isoforms.Journal of mass spectrometry : JMS · 2026Review
- Intact Proteoform Analysis by Capillary Electrophoresis-Mass Spectrometry. Are We There Yet?Angewandte Chemie (International ed. in English) · 2026Article
- Exercise-specific post-translational modification signatures: unveiling precise regulatory mechanisms of molecular exercise language and cellular adaptation.Frontiers in sports and active living · 2026Review
- PTM encoding: decoding the mechanisms of exercise-induced metabolic memory through spatiotemporal modification networks.Frontiers in sports and active living · 2026Review
- Quantitative Top-Down Proteomics Reveals Significant Differences in Histone Proteoforms Between Metastatic and Nonmetastatic Colorectal Cancer Cells.Proteomics · 2025Article
- Global Proteoform Alterations Across Multiple Cellular Compartments Underlie Obstructive Hypertrophic Cardiomyopathy.Circulation. Heart failure · 2025Article
- Bioinspired micro-structured fibers for biomedical applications.Bioactive materials · 2025Review
- A scalable proteogenomic framework for dissecting phospho-signaling pathways in primary immune cells.bioRxiv : the preprint server for biology · 2025Article
- High-Sensitivity Top-Down Proteomics Reveals Enhanced Maturation of Micropatterned Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Journal of proteome research · 2025Article
- Top-Down Proteomic Analysis of Limited Samples Using Porous Layer Open Tubular Columns and High-Field Asymmetric Ion Mobility Spectrometry Coupled to Mass Spectrometry.Analytical chemistry · 2025Article
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- Capillary Electrophoresis-Mass Spectrometry for Top-Down Proteomics.Annual review of analytical chemistry (Palo Alto, Calif.) · 2025Review
- Deciphering Proteoform Landscape of Mammary Carcinoma by Top-Down Proteomics.Journal of proteome research · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Single-cell proteomics has emerged as a powerful method to characterize cellular phenotypic heterogeneity and the cell-specific functional networks underlying biological processes. However, significant challenges remain in single-cell proteomics for the analysis of proteoforms arising from genetic mutations, alternative splicing, and post-translational modifications. Herein, we have developed a highly sensitive functionally integrated top-down proteomics method for the comprehensive analysis of proteoforms from single cells. We applied this method to single muscle fibers (SMFs) to resolve their heterogeneous functional and proteomic properties at the single-cell level. Notably, we have detected single-cell heterogeneity in large proteoforms (>200 kDa) from the SMFs. Using SMFs obtained from three functionally distinct muscles, we found fiber-to-fiber heterogeneity among the sarcomeric proteoforms which can be related to the functional heterogeneity. Importantly, we detected multiple isoforms of myosin heavy chain (~223 kDa), a motor protein that drives muscle contraction, with high reproducibility to enable the classification of individual fiber types. This study reveals single muscle cell heterogeneity in large proteoforms and establishes a direct relationship between sarcomeric proteoforms and muscle fiber types, highlighting the potential of top-down proteomics for uncovering the molecular underpinnings of cell-to-cell variation in complex systems.
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