iScience (May 2023)
Large-scale microRNA functional high-throughput screening identifies miR-515-3p and miR-519e-3p as inducers of human cardiomyocyte proliferation
- Harsha V. Renikunta,
- Katina Lazarow,
- Yiqi Gong,
- Praphulla Chandra Shukla,
- Vanasa Nageswaran,
- Hector Giral,
- Adelheid Kratzer,
- Lennart Opitz,
- Felix B. Engel,
- Arash Haghikia,
- Sarah Costantino,
- Francesco Paneni,
- Jens Peter von Kries,
- Katrin Streckfuss-Bömeke,
- Ulf Landmesser,
- Philipp Jakob
Affiliations
- Harsha V. Renikunta
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany
- Katina Lazarow
- Leibniz-Institute for Molecular Pharmacology (FMP), Campus Berlin-Buch, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
- Yiqi Gong
- Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland
- Praphulla Chandra Shukla
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, West Bengal, India
- Vanasa Nageswaran
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany; Institute of Chemistry/Biochemistry, Thielallee 63, Freie Universität Berlin, 14195 Berlin, Germany
- Hector Giral
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Adelheid Kratzer
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Lennart Opitz
- Functional Genomics Center Zurich UZH/ETH, ETH Zurich and University of Zurich, 8057 Zurich, Switzerland
- Felix B. Engel
- Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 12 (TRC), 91054 Erlangen, Germany
- Arash Haghikia
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany; Berlin Institute of Health (BIH) at Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Sarah Costantino
- Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland
- Francesco Paneni
- Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland
- Jens Peter von Kries
- Leibniz-Institute for Molecular Pharmacology (FMP), Campus Berlin-Buch, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
- Katrin Streckfuss-Bömeke
- Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Robert-Koch-Strasse 42a, 37075 Göttingen, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany
- Ulf Landmesser
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany; Berlin Institute of Health (BIH) at Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Philipp Jakob
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland; Berlin Institute of Health (BIH) at Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Corresponding author
- Journal volume & issue
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Vol. 26,
no. 5
p. 106593
Abstract
Summary: Ischemic cardiomyopathy, driven by loss of cardiomyocytes and inadequate proliferative response, persists to be a major global health problem. Using a functional high-throughput screening, we assessed differential proliferative potential of 2019 miRNAs after transient hypoxia by transfecting both miR-inhibitor and miR-mimic libraries in human iPSC-CM. Whereas miR-inhibitors failed to enhance EdU uptake, overexpression of 28 miRNAs substantially induced proliferative activity in hiPSC-CM, with an overrepresentation of miRNAs belonging to the primate-specific C19MC-cluster. Two of these miRNAs, miR-515-3p and miR-519e-3p, increased markers of early and late mitosis, indicative of cell division, and substantially alter signaling pathways relevant for cardiomyocyte proliferation in hiPSC-CM.
