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c-kit+ cells minimally contribute cardiomyocytes to the heart.

van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin SC, Middleton RC, Marbán E, Molkentin JD - Nature (2014)

Bottom Line: Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008.By contrast, c-kit(+) cells amply generated cardiac endothelial cells.Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Department of Medicine, division of Cardiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA [3].

ABSTRACT
If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.

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Assessing cardiomyocyte differentiation markers from total non-myocytes in the heartAdult cardiac interstitial cells isolated from a Kit+/Cre × R-GFP mouse were treated with dexamethasone for 1 week. Cells were then fixed and subjected to immunocytochemistry for the indicated antibodies. c-kit lineage derived cells were green (eGFP+) and showed fluorescence in the cytosol and nucleus. The data show eGFP cells that express markers of differentiated cardiomyocytes such as α-actinin, troponin T, and the transcription factor GATA4 (all in red) but not the fibroblast marker vimentin (white), nuclei were stained blue (right panels). These results indicate that eGFP+Kit-Cre expressing cells can generate pre-differentiated cardiomyocytes as well as non-eGFP interstitial cells; hence the cells identified by the Kit-Cre (knock-in) reporter strategy are representative of how endogenous c-kit+ expressing cells truly function.
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Figure 13: Assessing cardiomyocyte differentiation markers from total non-myocytes in the heartAdult cardiac interstitial cells isolated from a Kit+/Cre × R-GFP mouse were treated with dexamethasone for 1 week. Cells were then fixed and subjected to immunocytochemistry for the indicated antibodies. c-kit lineage derived cells were green (eGFP+) and showed fluorescence in the cytosol and nucleus. The data show eGFP cells that express markers of differentiated cardiomyocytes such as α-actinin, troponin T, and the transcription factor GATA4 (all in red) but not the fibroblast marker vimentin (white), nuclei were stained blue (right panels). These results indicate that eGFP+Kit-Cre expressing cells can generate pre-differentiated cardiomyocytes as well as non-eGFP interstitial cells; hence the cells identified by the Kit-Cre (knock-in) reporter strategy are representative of how endogenous c-kit+ expressing cells truly function.


c-kit+ cells minimally contribute cardiomyocytes to the heart.

van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin SC, Middleton RC, Marbán E, Molkentin JD - Nature (2014)

Assessing cardiomyocyte differentiation markers from total non-myocytes in the heartAdult cardiac interstitial cells isolated from a Kit+/Cre × R-GFP mouse were treated with dexamethasone for 1 week. Cells were then fixed and subjected to immunocytochemistry for the indicated antibodies. c-kit lineage derived cells were green (eGFP+) and showed fluorescence in the cytosol and nucleus. The data show eGFP cells that express markers of differentiated cardiomyocytes such as α-actinin, troponin T, and the transcription factor GATA4 (all in red) but not the fibroblast marker vimentin (white), nuclei were stained blue (right panels). These results indicate that eGFP+Kit-Cre expressing cells can generate pre-differentiated cardiomyocytes as well as non-eGFP interstitial cells; hence the cells identified by the Kit-Cre (knock-in) reporter strategy are representative of how endogenous c-kit+ expressing cells truly function.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127035&req=5

Figure 13: Assessing cardiomyocyte differentiation markers from total non-myocytes in the heartAdult cardiac interstitial cells isolated from a Kit+/Cre × R-GFP mouse were treated with dexamethasone for 1 week. Cells were then fixed and subjected to immunocytochemistry for the indicated antibodies. c-kit lineage derived cells were green (eGFP+) and showed fluorescence in the cytosol and nucleus. The data show eGFP cells that express markers of differentiated cardiomyocytes such as α-actinin, troponin T, and the transcription factor GATA4 (all in red) but not the fibroblast marker vimentin (white), nuclei were stained blue (right panels). These results indicate that eGFP+Kit-Cre expressing cells can generate pre-differentiated cardiomyocytes as well as non-eGFP interstitial cells; hence the cells identified by the Kit-Cre (knock-in) reporter strategy are representative of how endogenous c-kit+ expressing cells truly function.
Bottom Line: Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008.By contrast, c-kit(+) cells amply generated cardiac endothelial cells.Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Department of Medicine, division of Cardiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA [3].

ABSTRACT
If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.

Show MeSH
Related in: MedlinePlus