title: PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium.
abstract: Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα(+) cells. Clonal progeny of single Sca1(+) SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα(-) cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα(+)/CD31(-) cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα(-)/CD31(+) cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1(+) stem/progenitor cell.
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Michela
authors.initials: M
authors.lastname: Noseda
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harada
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: McSweeney
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Leja
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Elisa
authors.initials: E
authors.lastname: Belian
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK [3] Centre for Advanced Biomedical Imaging (CABI), University College London, London WC1E 6DD, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stuckey
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Marta S
authors.initials: MS
authors.lastname: Abreu Paiva
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK [3] Department of Biomedical Engineering, King's College London, London SE1 7EH, UK.
authors.forename: Josef
authors.initials: J
authors.lastname: Habib
authors.affiliation: Haematopoietic Stem Cell Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Macaulay
authors.affiliation: 1] Department of Medicine, Imperial College London, London SW7 2AZ, UK [2] Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: de Smith
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Farah
authors.initials: F
authors.lastname: al-Beidh
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Sampson
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Lumbers
authors.affiliation: 1] Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Pulivarthi
authors.initials: P
authors.lastname: Rao
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Sian E
authors.initials: SE
authors.lastname: Harding
authors.affiliation: Department of Medicine, Imperial College London, London SW7 2AZ, UK.
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.affiliation: Haematopoietic Stem Cell Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Sten Eirik
authors.initials: SE
authors.lastname: Jacobsen
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] Department of Mathematics, Imperial College London, London SW7 2AZ, UK.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Barahona
authors.affiliation: 1] British Heart Foundation Centre of Research Excellence, Imperial College London, London SW7 2AZ, UK [2] National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schneider
mesh_terms: D000818:Animals; D000067696:Ataxin-1 / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D025341:Principal Component Analysis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D020825:T-Box Domain Proteins / Q000235:genetics
chemical_list: D000067696:Ataxin-1; D051792:Basic Helix-Loop-Helix Proteins; D050991:GATA4 Transcription Factor; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020825:T-Box Domain Proteins; C000593750:Atxn1 protein, mouse; C484171:Gata4 protein, mouse; C498766:Hand2 protein, mouse; C103172:T-box transcription factor 5