Role of the lipid sensor PPAR-gamma in cardiac progenitor cell deployment: First demonstration of the impact of environmental factor on cardiac progenitor cell development - 25/09/20
Résumé |
Introduction |
One third of the life-threatening congenital heart diseases (CHD) affects the conotruncal region that connect the ventricles to the great arteries. This region originates from the Second Heart Field (SHF) progenitors that contribute to the heart tube elongation giving rise to the last cardiomyocytes adding to the right ventricle. SHF deployment is thus crucial for the normal heart development. Previously, we have demonstrated that this process requires master transcription factors and signaling pathways including TBX1 and NOTCH/HES1, any alteration of which results in failure of the outflow tract (OFT) to correctly elongate and divide. By performing gene expression profiling at mid-gestation we defined the transcriptional program of future sub-aortic and sub-pulmonary myocardium and identified the lipid sensor Pparg as an upstream regulator of the cross-circuitry regulating regional identity in the superior and inferior OFT walls.
Aims |
Deciphering the role of Pparg in the early heart development and CHD related to maternal obesity.
Methods |
We investigate the spatiotemporal expression of genes involved in the Pparg pathway in wildtype and mutant Pparg mouse lines and determine the influence of maternal obesity in embryos recovered from in high-fat diet treated mothers.
Results |
We demonstrated that Pparg is required for the OFT morphogenesis. Interestingly, we observed that SHF and OFT cells are competent to uptake external fatty acids and that excess of maternal fatty acid leads to CHD. Indeed, 22% of foetuses from obese mothers displayed CHDs supporting large scale human investigations pointing to maternal obesity as an important risk for severe CHD affecting the OFT region.
Conclusion |
These results suggest for the first time that environmental factors impact on SHF development. We are thus exploring further this hypothesis addressing the role of Pparg as a metabolic regulator affecting OFT patterning under condition of HFD-induced maternal obesity.
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Vol 12 - N° 2-4
P. 220-221 - octobre 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.