Microscopy-based single-cell proteomic profiling reveals heterogeneity in DNA damage response dynamics
Pin Rui Su (Erasmus MC, National Taiwan University)
Li You (Erasmus MC)
Cecile Beerens (Erasmus MC)
Karel Bezstarosti (Erasmus MC)
Jeroen Demmers (Erasmus MC)
Martin Pabst (TU Delft - Applied Sciences)
Roland Kanaar (Erasmus MC, TU Delft - Applied Sciences, The Oncode Institute)
Cheng Chih Hsu (National Taiwan University)
Miao Ping Chien (TU Delft - Applied Sciences, The Oncode Institute, Erasmus MC)
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Abstract
Single-cell proteomics has the potential to decipher tumor heterogeneity, and a method like single-cell proteomics by mass spectrometry (SCoPE-MS) allows profiling several tens of single cells for >1,000 proteins per cell. This method, however, cannot link the proteome of individual cells with phenotypes of interest. Here, we developed a microscopy-based functional single-cell proteomic-profiling technology, called FUNpro, to address this. FUNpro enables screening, identification, and isolation of single cells of interest in a real-time fashion, even if the phenotypes are dynamic or the cells of interest are rare. We applied FUNpro to proteomically profile a newly identified small subpopulation of U2OS osteosarcoma cells displaying an abnormal, prolonged DNA damage response (DDR) after ionizing radiation (IR). With this, we identified the PDS5A protein contributing to the abnormal DDR dynamics and helping the cells survive after IR.
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