Surfaceome mapping of primary human heart cells with CellSurfer uncovers cardiomyocyte surface protein LSMEM2 and proteome dynamics in failing hearts

Cardiac cell surface proteins are drug targets and useful biomarkers for discriminating among cellular phenotypes and disease states. Here we developed an analytical platform, CellSurfer, that enables quantitative cell surface proteome (surfaceome) profling of cells present in limited quantities, and we apply it to isolated primary human heart cells. We report experimental evidence of surface localization and extracellular domains for 1,144 N-glycoproteins, including cell-type-restricted and region-restricted glycoproteins. We identifed a surface protein specifc for healthy cardiomyocytes, LSMEM2, and validated an anti-LSMEM2 monoclonal antibody for fow cytometry and imaging. Surfaceome comparisons among pluripotent stem cell derivatives and their primary counterparts highlighted important diferences with direct implications for drug screening and disease modeling. Finally, 20% of cell surface proteins, including LSMEM2, were diferentially abundant between failing and nonfailing cardiomyocytes. These results represent a rich resource to advance development of cell type and organ-specifc targets for drug delivery, disease modeling, immunophenotyping and in vivo imaging