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Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin

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    Rights statement: Published in final edited form as: Nat Genet. 2010 January ; 42(1): 89–93. doi:10.1038/ng.494.

    Accepted author manuscript, 1.89 MB, PDF document

http://www.nature.com/ng/journal/v42/n1/full/ng.494.html#affil-auth
Original languageEnglish
Pages (from-to)89-93
Number of pages5
JournalNature Genetics
Volume42
Issue number1
DOIs
Publication statusPublished - 2010

Abstract

The epicardial epithelial-mesenchymal transition (EMT) is hypothesized to generate cardiovascular progenitor cells that differentiate into various cell types, including coronary smooth muscle and endothelial cells, perivascular and cardiac interstitial fibroblasts and cardiomyocytes. Here we show that an epicardial-specific knockout of the gene encoding Wilms' tumor-1 (Wt1) leads to a reduction in mesenchymal progenitor cells and their derivatives. We show that Wt1 is essential for repression of the epithelial phenotype in epicardial cells and during embryonic stem cell differentiation through direct transcriptional regulation of the genes encoding Snail (Snai1) and E-cadherin (Cdh1), two of the major mediators of EMT. Some mesodermal lineages do not form in Wt1-null embryoid bodies, but this effect is rescued by the expression of Snai1, underscoring the importance of EMT in generating these differentiated cells. These new insights into the molecular mechanisms regulating cardiovascular progenitor cells and EMT will shed light on the pathogenesis of heart diseases and may help the development of cell-based therapies.

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