PDGFRα demarcates the cardiogenic clonogenic Sca1(+) stem/progenitor cell in adult murine myocardium
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Published version
Author(s)
Type
Journal Article
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.
Date Issued
2015-05-18
Date Acceptance
2015-03-16
Citation
Nature Communications, 2015, 6 (4)
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
6
Issue
4
Copyright Statement
© 2015 The Author(s). This work is licensed under a Creative Commons Attribution 4.0
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
License URL
Sponsor
British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
Commission of the European Communities
The Royal Society
Commission of the European Communities
British Heart Foundation
British Heart Foundation
Commission of the European Communities
British Heart Foundation
British Heart Foundation
Medical Research Council (MRC)
British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
Identifier
PII: ncomms7930
Grant Number
RE/13/4/30184
RG/15/1/31165
CH/08/002/25297
RE/08/002/23906
330912
502011.K501/je
223372
SI/11/2/28875
CH/08/002
NO 233158
RG/08/007
RG/11/19/29264
G0901467
RG/08/007/25296
CH/08/002/25297
RM/17/1/33377
FS/14/62/31288
RG/14/1/30588
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CARDIAC STEM-CELLS
SIDE POPULATION CELLS
PROGENITOR CELLS
SMOOTH-MUSCLE
PRESSURE-OVERLOAD
HEART REPAIR
CARDIOMYOCYTES
MULTIPOTENT
EXPRESSION
FATE
Animals
Ataxin-1
Basic Helix-Loop-Helix Transcription Factors
Cell Differentiation
Cell Lineage
Endothelial Cells
Female
GATA4 Transcription Factor
Gene Expression Regulation
Male
Mice
Mice, Inbred C57BL
Myocardium
Myocytes, Cardiac
Myocytes, Smooth Muscle
Phenotype
Platelet Endothelial Cell Adhesion Molecule-1
Principal Component Analysis
Receptor, Platelet-Derived Growth Factor alpha
Regeneration
Stem Cells
T-Box Domain Proteins
Myocardium
Endothelial Cells
Myocytes, Cardiac
Myocytes, Smooth Muscle
Stem Cells
Animals
Mice, Inbred C57BL
Mice
Receptor, Platelet-Derived Growth Factor alpha
T-Box Domain Proteins
Regeneration
Cell Differentiation
Gene Expression Regulation
Cell Lineage
Phenotype
Principal Component Analysis
Female
Male
GATA4 Transcription Factor
Basic Helix-Loop-Helix Transcription Factors
Ataxin-1
Platelet Endothelial Cell Adhesion Molecule-1
Publication Status
Published
Article Number
ARTN 6930