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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number884
JournalCommunications Biology
Volume7
Issue number1
DOIs
StatePublished - Dec 2024

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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