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

Autor: Luecke LB; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA., Waas M; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.; Present address: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Littrell J; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA., Wojtkiewicz M; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA., Castro C; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA., Burkovetskaya M; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA., Schuette EN; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA., Buchberger AR; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA.; Present address: Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA., Churko JM; Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA., Chalise U; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA., Waknitz M; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA., Konfrst S; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA., Teuben R; Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA., Morrissette-McAlmon J; Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA., Mahr C; Department of Mechanical Engineering, Division of Cardiology, University of Washington, Seattle, WA, USA., Anderson DR; Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA., Boheler KR; Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA.; Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, MD, USA., Gundry RL; CardiOmics Program, Center for Heart and Vascular Research and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.; Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2023 Jan; Vol. 2 (1), pp. 76-95. Date of Electronic Publication: 2023 Jan 16.
DOI: 10.1038/s44161-022-00200-y
Abstrakt: 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.
Competing Interests: Competing interests R.L.G. is on the advisory board of ProtiFi, LLC, and receives no compensation of any kind for this role. The other authors declare no competing interests.
Databáze: MEDLINE
Externí odkaz: