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

Linda Berg Luecke, Matthew Waas, Jack Littrell, Melinda Wojtkiewicz, Chase Castro, Maria Burkovetskaya, Erin N. Schuette, Amanda Rae Buchberger, Jared M. Churko, Upendra Chalise, Michelle Waknitz, Shelby Konfrst, Roald Teuben, Justin Morrissette-McAlmon, Claudius Mahr, Daniel R. Anderson, Kenneth R. Boheler, Rebekah L. Gundry

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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) profiling 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 identified a surface protein specific for healthy cardiomyocytes, LSMEM2, and validated an anti-LSMEM2 monoclonal antibody for flow cytometry and imaging. Surfaceome comparisons among pluripotent stem cell derivatives and their primary counterparts highlighted important differences with direct implications for drug screening and disease modeling. Finally, 20% of cell surface proteins, including LSMEM2, were differentially abundant between failing and non-failing cardiomyocytes. These results represent a rich resource to advance development of cell type and organ-specific targets for drug delivery, disease modeling, immunophenotyping and in vivo imaging.

Original languageEnglish (US)
Pages (from-to)76-95
Number of pages20
JournalNature Cardiovascular Research
Volume2
Issue number1
DOIs
StatePublished - Jan 2023

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology
  • Medicine (miscellaneous)
  • Cardiology and Cardiovascular Medicine

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