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Diversity of post-translational modifications and cell signaling revealed by single cell and single organelle mass spectrometry

  • Dong-Gi Mun,
  • Firdous A. Bhat,
  • Neha Joshi,
  • Leticia Sandoval,
  • Husheng Ding,
  • Anu Jain,
  • Jane A. Peterson,
  • Taewook Kang,
  • Ganesh P. Pujari,
  • Jennifer L. Tomlinson,
  • Rohit Budhraja,
  • Roman M. Zenka,
  • Nagarajan Kannan,
  • Benjamin R. Kipp,
  • Surendra Dasari,
  • Alexandre Gaspar-Maia,
  • Rory L. Smoot,
  • Richard K. Kandasamy,
  • Akhilesh Pandey

摘要

The rapid evolution of mass spectrometry-based single-cell proteomics now enables the cataloging of several thousand proteins from single cells. We investigated whether we could discover cellular heterogeneity beyond proteome, encompassing post-translational modifications (PTM), protein-protein interaction, and variants. By optimizing the mass spectrometry data interpretation strategy to enable the detection of PTMs and variants, we have generated a high-definition dataset of single-cell and nuclear proteomic-states. The data demonstrate the heterogeneity of cell-states and signaling dependencies at the single-cell level and reveal epigenetic drug-induced changes in single nuclei. This approach enables the exploration of previously uncharted single-cell and organellar proteomes revealing molecular characteristics that are inaccessible through RNA profiling.