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Abcg2-Expressing Side Population Cells Contribute to Cardiomyocyte Renewal through Fusion
- Source :
- FASEB J
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- The adult mammalian heart has a limited regenerative capacity. Therefore, identification of endogenous cells and mechanisms that contribute to cardiac regeneration is essential for the development of targeted therapies. The side population (SP) phenotype has been used to enrich for stem cells throughout the body; however, SP cells isolated from the heart have been studied exclusively in cell culture or after transplantation, limiting our understanding of their function in vivo. We generated a new Abcg2-driven lineage-tracing mouse model with efficient labeling of SP cells. Labeled SP cells give rise to terminally differentiated cells in bone marrow and intestines. In the heart, labeled SP cells give rise to lineage-traced cardiomyocytes under homeostatic conditions with an increase in this contribution following cardiac injury. Instead of differentiating into cardiomyocytes like proposed cardiac progenitor cells, cardiac SP cells fuse with preexisting cardiomyocytes to stimulate cardiomyocyte cell cycle reentry. Our study is the first to show that fusion between cardiomyocytes and non-cardiomyocytes, identified by the SP phenotype, contribute to endogenous cardiac regeneration by triggering cardiomyocyte cell cycle reentry in the adult mammalian heart.
- Subjects :
- Male
0301 basic medicine
Abcg2
Cellular differentiation
Myocardial Ischemia
Endogeny
030204 cardiovascular system & hematology
Biochemistry
Article
Mice
03 medical and health sciences
0302 clinical medicine
Side population
Genetics
medicine
ATP Binding Cassette Transporter, Subfamily G, Member 2
Animals
Regeneration
Cell Lineage
Myocytes, Cardiac
Side-Population Cells
Molecular Biology
Cells, Cultured
Bone Marrow Transplantation
030304 developmental biology
Mice, Knockout
0303 health sciences
biology
Cell Differentiation
Cell cycle
Phenotype
Cell biology
Transplantation
030104 developmental biology
medicine.anatomical_structure
biology.protein
Female
Bone marrow
Stem cell
030217 neurology & neurosurgery
Homeostasis
Biotechnology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- FASEB J
- Accession number :
- edsair.doi.dedup.....6fbc1e0e2f0861857bae7d110b16d68e