scholarly journals YY1 Expression Is Sufficient for the Maintenance of Cardiac Progenitor Cell State

Stem Cells ◽  
2017 ◽  
Vol 35 (8) ◽  
pp. 1913-1923 ◽  
Author(s):  
Serge Gregoire ◽  
Guang Li ◽  
Anthony C. Sturzu ◽  
Robert J. Schwartz ◽  
Sean M. Wu
Keyword(s):  
Progenitor Cell ◽  
Cardiac Progenitor Cell ◽  
Cell State

scholarly journals Human Cardiac Progenitor Cell Grafts as Unrestricted Source of Supernumerary Cardiac Cells in Healthy Murine Hearts

Stem Cells ◽  
2011 ◽  
Vol 29 (12) ◽  
pp. 2051-2061 ◽  
Author(s):  
Giancarlo Forte ◽  
Stefano Pietronave ◽  
Giorgia Nardone ◽  
Andrea Zamperone ◽  
Eugenio Magnani ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Cardiac Cells ◽  
Cardiac Progenitor Cell

scholarly journals Accumulation of mitochondrial DNA mutations disrupts cardiac progenitor cell function and reduces survival

2017 ◽  
Vol 292 (27) ◽  
pp. 11348-11348
Author(s):  
Amabel M. Orogo ◽  
Eileen R. Gonzalez ◽  
Dieter A. Kubli ◽  
Igor L. Baptista ◽  
Sang-Bing Ong ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Progenitor Cell ◽  
Cell Function ◽  
Cardiac Progenitor Cell ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations

Abstract 340: Short Telomeres Induce Autophagy and Modulate Cardiac Progenitor Cell Fate

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Nirmala Hariharan ◽  
Collin Matsumoto ◽  
Jacqueline Emathinger ◽  
Saba Daneshpooy ◽  
Minyoung Shin ◽  
...  
Keyword(s):  
Cell Fate ◽  
Progenitor Cell ◽  
Smooth Muscle Actin ◽  
Wild Mouse ◽  
Degradation Process ◽  
Mouse Strains ◽  
Therapeutic Effects ◽  
Cardiac Progenitor Cell ◽  
Altered Cell ◽  
The Impact

Aging severely limits myocardial regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesize that short telomeres induce autophagy and elicit the age-associated change in cardiac progenitor cell fate. We compared mouse strains with different telomere lengths (TL) for phenotypic characteristics of aging and also isolated CPCs from them. Naturally occurring wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres (TL:18Kb) exhibits early cardiac aging with diastolic dysfunction, hypertrophy, fibrosis and increase in senescence markers p53 and p16, as compared to common lab strains FVB (TL:75Kb) and C57 (TL:50Kb). CAST CPCs with short TLs have altered cell fate as characterized by slower proliferation (p<0.01); increased senescence identified by beta-galactosidase activity (p<0.05); increased basal commitment as determined by expression of lineage markers smooth muscle actin, Tie2, and sarcomeric actinin (16.6, 1.7 and 1.75, p<0.05); as well as loss of quiescence marker expression. Consistent findings of altered cell fate are also evident in old CPCs isolated from aged mice with significantly shorter TLs. Cell fate changes occurring downstream from short TL are at least partially p53 dependent, as p53 inhibition rescues the irreversible cell cycle arrest observed in CAST CPCs. Mechanistically, short TLs induce autophagy, a catabolic protein degradation process. Autophagy flux is increased in CAST CPCs as evidenced by increased LC3 (p<0.05), reduced p62 expression (-52%, p<0.05) and increased accumulation of autophagic puncta. Pharmacological inhibition of autophagosome formation, but not autolysosome formation reverses the cell fate to a more youthful phenotype. Overall the data suggests that short TLs activate autophagy to accommodate cell fate changes that tip the equilibrium away from quiescence and proliferation into differentiation and senescence, leading to age-associated exhaustion of CPCs. The study provides the mechanistic basis underlying age-associated cell fate changes that will enable identification of molecular strategies to enhance the therapeutic effects of aged CPCs.

Abstract 297: Nkx2–5 Transcriptionally Activates C-kit-ligand And Regulates Cardiac Progenitor Cell Populations

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rebecca L Scotland ◽  
Xiaozhong Shi ◽  
Anwarul Ferdous ◽  
Michael Kyba ◽  
Daniel J Garry
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Progenitor Cell ◽  
Transcriptional Regulator ◽  
Luciferase Reporter ◽  
Transcriptional Networks ◽  
Cell Populations ◽  
Cardiac Progenitor Cell ◽  
Downstream Target ◽  
Kit Ligand

C-kit-ligand, also known as stem cell factor, is expressed broadly and has a functional role during hematopoesis, gametogenesis, melanogenesis, mast cell growth and differentiation. Although the receptor for c-kit-ligand, c-kit, has been utilized as a marker to identify cardiac stem cell and progenitor cell populations, the transcriptional regulation and biological function of c-kit-ligand during cardiogenesis has not been defined. Here we demonstrate that c-kit-ligand is a novel downstream target of Nkx2–5. The homeodomain transcription factor, Nkx2–5, is one of the earliest markers of the cardiac lineage and mice lacking this transcription factor are nonviable. To identify potential Nkx2–5 downstream target genes, we utilized ES/EBs that were engineered to overexpress Nkx2–5 and undertook transcriptome analysis of embyroid bodies with and without Nkx2–5 induction. We observed a significant increase in c-kit-ligand expression following Nkx2–5 induction suggesting a role for Nkx2–5 in the activation of c-kit-ligand. Furthermore, analysis of the c-kit-ligand promoter revealed three evolutionarily conserved Nkx2–5 response elements, supporting the notion that Nkx2–5 is a transcriptional regulator of gene expression. We undertook transcriptional assays and transfected the c-kit-ligand promoter-luciferase reporter in the absence and presence of increasing amounts of Nkx2–5. We observed that Nkx2–5, in a dose dependent fashion, was a potent transcriptional activator of c-kit-ligand. These studies enhance our understanding of Nkx2–5 mediated transcriptional networks and further emphasize that Nkx2–5 is an important transcriptional regulator of cardiac progenitor cell populations.

scholarly journals Irisin promotes cardiac progenitor cell-induced myocardial repair and functional improvement in infarcted heart

2018 ◽  
Vol 234 (2) ◽  
pp. 1671-1681 ◽  
Author(s):  
Yu Tina Zhao ◽  
Jianguo Wang ◽  
Naohiro Yano ◽  
Ling X. Zhang ◽  
Hao Wang ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Functional Improvement ◽  
Myocardial Repair ◽  
Cardiac Progenitor Cell ◽  
Infarcted Heart

Abstract 356: Krueppel-Like Factor 15 Regulates Wnt/β-Catenin Transcription and Controls Cardiac Progenitor Cell Fate in the Postnatal Heart

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Claudia Noack ◽  
Maria P Zafiriou ◽  
Anke Renger ◽  
Hans J Schaeffer ◽  
Martin W Bergmann ◽  
...  
Keyword(s):  
Cell Fate ◽  
Transcriptional Activation ◽  
Progenitor Cell ◽  
Cellular Localization ◽  
Target Genes ◽  
Critical Role ◽  
Isolated Cells ◽  
Cardiac Progenitor Cell

Wnt/β-catenin signaling controls adult heart remodeling partly by regulating cardiac progenitor cell (CPC) differentiation. We now identified and characterized a novel cardiac interaction of the transcription factor Krueppel-like factor 15 (KLF15) with the Wnt/β-catenin signaling on adult CPCs. In vitro mutation, reporter gene assays and co-localization studies revealed that KLF15 requires two distinct domains for nuclear localization and for repression of β-catenin-mediated transcription. KLF15 had no effect on β-catenin stability or cellular localization, but interacted with its co-factor TCF4, which is required for activation of β-catenin target gene expression. Moreover, increased TCF4 ubiquitination was induced by KLF15. In line with this finding we found KLF15 to interact with the Nemo-like kinase, which was shown to phosphorylate and target TCF4 for degradation. In vivo analyses of adult Klf15 functional knock-out (KO) vs. wild-type (WT) mice showed a cardiac β-catenin-mediated transcriptional activation and reduced TCF4 degradation along with cardiac dysfunction assessed by echocardiography (n=10). FACS analysis of the CPC enriched-population of KO vs. WT mice revealed a significant reduction of cardiogenic-committed precursors identified as Sca1+/αMHC+ (0.8±0.2% vs. 1.8±0.1%) and Tbx5+ (3.5±0.3% vs. 5.2±0.5%). In contrast, endothelial Sca1+/CD31+ cells were significantly higher in KO mice (11.3±0.4% vs. 8.6±0.4%; n≥9). In addition, Sca1+ isolated cells of Klf15 KO showed increased RNA expression of endothelial markers von Willebrand Factor, CD105, and Flk1 along with upregulation of β-catenin target genes. CPCs co-cultured on adult fibroblasts resulted in increased endothelial Flk1 cells and reduction of αMHC and Hand1 cardiogenic cells in KO vs. WT CPCs (n=9). Treating these co-cultures with Quercetin, an inhibitor of nuclear β-catenin, resulted in partial rescue of the observed phenotype. This study uncovers a critical role of KLF15 for the maintenance of cardiac tissue homeostasis. Via inhibition of β-catenin transcription, KLF15 controls cardiomyogenic cell fate similar to embryonic cardiogenesis. This knowledge may provide a tool for activation of endogenous CPCs in the postnatal heart.

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