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

Commun Biol. 2024 Jul 19;7(1):884. doi: 10.1038/s42003-024-06579-7.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Mass Spectrometry* / methods
  • Organelles / metabolism
  • Protein Processing, Post-Translational*
  • Proteome / metabolism
  • Proteomics* / methods
  • Signal Transduction*
  • Single-Cell Analysis* / methods

Substances

  • Proteome