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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Fibrogenic Potential of PW1/Peg3 Expressing Cardiac Stem Cells
Elisa Yaniz-Galende1, Maguelonne Roux1, Sophie Nadaud1
1Sorbonne-Universités, Université Pierre-et-Marie-Curie (UPMC), INSERM UMRS_1166, Institute of Cardiometabolism and Nutrition, Paris, France.
Insights
PW1-expressing cardiac stem cells are identified and characterized. These cells contribute to fibrotic remodeling after myocardial infarction (MI), differentiating into fibroblasts rather than cardiomyocytes.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Regenerative Medicine
Background:
- PW1 gene expression marks adult stem cells across various tissues.
- PW1-expressing cells exist in the heart but require further characterization.
Purpose of the Study:
- To characterize cardiac PW1-expressing cells and their differentiation potential.
- To investigate their role in cardiac remodeling post-myocardial infarction (MI).
Main Methods:
- Utilized a PW1 reporter mouse model (PW1nLacZ+/-) for cell identification and tracking.
- Analyzed human cardiac samples and mouse hearts under normal and ischemic conditions post-MI.
- Isolated PW1-expressing cells to assess their differentiation capacity.
Main Results:
- PW1 expression was prominent in infarct and border zones of ischemic hearts (human and mouse).
- Isolated PW1+ cells formed colonies and differentiated into fibroblast-like cells, not cardiomyocytes.
- Lineage tracing confirmed PW1+ cell differentiation into fibroblasts post-MI.
- Co-expression of c-Kit and PW1 increased significantly in ischemic hearts, with c-Kit+/PW1+ cells being fibrogenic.
Conclusions:
- A novel population of resident adult cardiac stem cells expressing PW1 has been identified.
- These PW1+ cells play a role in the fibrotic remodeling process following myocardial infarction.
Background:
Pw1 gene expression is a marker of adult stem cells in a wide range of tissues. PW1-expressing cells are detected in the heart but are not well characterized.
Objectives:
The authors characterized cardiac PW1-expressing cells and their cell fate potentials in normal hearts and during cardiac remodeling following myocardial infarction (MI).
Methods:
A human cardiac sample was obtained from a patient presenting with reduced left ventricular (LV) function following a recent MI. The authors used the PW1nLacZ+/- reporter mouse to identify, track, isolate, and characterize PW1-expressing cells in the LV myocardium in normal and ischemic conditions 7 days after complete ligature of the left anterior descending coronary artery.
Results:
In both human and mouse ischemic hearts, PW1 expression was found in cells that were mainly located in the infarct and border zones. Isolated cardiac resident PW1+ cells form colonies and have the potential to differentiate into multiple cardiac and mesenchymal lineages, with preferential differentiation into fibroblast-like cells but not into cardiomyocytes. Lineage-tracing experiments revealed that PW1+ cells differentiated into fibroblasts post-MI. Although the expression of c-Kit and PW1 showed little overlap in normal hearts, a marked increase in cells coexpressing both markers was observed in ischemic hearts (0.1 ± 0.0% in control vs. 5.7 ± 1.2% in MI; p < 0.001). In contrast to the small proportion of c-Kit+/PW1- cells that showed cardiogenic potential, c-Kit+/PW1+ cells were fibrogenic.
Conclusions:
This study demonstrated the existence of a novel population of resident adult cardiac stem cells expressing PW1+ and their involvement in fibrotic remodeling after MI.

