Diversity of post-translational modifications and cell signaling revealed by single cell and single organelle mass spectrometry.
Dong-Gi MunFirdous A BhatNeha S JoshiLeticia SandovalHusheng DingAnu JainJane A PetersonTaewook KangGanesh P PujariJennifer L TomlinsonRohit BudhrajaRoman M ZenkaNagarajan KannanBenjamin R KippSurendra DasariAlexandre Gaspar-MaiaRory L SmootRichard Kumaran KandasamyAkhilesh PandeyPublished in: Communications biology (2024)
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.
Keyphrases
- single cell
- mass spectrometry
- rna seq
- high throughput
- liquid chromatography
- protein protein
- high resolution
- gas chromatography
- high performance liquid chromatography
- capillary electrophoresis
- gene expression
- copy number
- label free
- electronic health record
- big data
- dna methylation
- induced apoptosis
- emergency department
- loop mediated isothermal amplification
- stem cells
- machine learning
- oxidative stress
- tandem mass spectrometry
- cell proliferation
- cell cycle arrest
- adverse drug
- signaling pathway
- mesenchymal stem cells
- genome wide