title: miR302 regulates SNAI1 expression to control mesangial cell plasticity.
abstract: Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation. esiRNA silencing of each component suggest that Smad3 and EZH2 are part of a complex that regulates plasticity and that miR302 regulates EZH2 and Snail independently. Subsequent manipulation of miR302 overexpressing cells demonstrated the potential of using this approach for reprogramming as evidenced by de novo expression of the tight junction components ZO-1 and E-cadherin and the formation of ZO-1 containing tight junctions. Understanding the processes through which dynamic epigenetic silencing is controlled in adults cells will allow us to address the epigenetic state of acquired disease and whether original states, regenerative in nature, can be restored with therapy.
authors.affiliation: UCD Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland.|UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.|Weill Cornell Medical College (WCMC), Department of Surgery, 1300 York Avenue, 10065 New York (NY), USA.
authors.forename: L
authors.initials: L
authors.lastname: De Chiara
authors.affiliation: UCD Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland.|UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Andrews
authors.affiliation: UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Watson
authors.affiliation: UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.|Syddansk Universitet - Odense Universitet Institut for Biokemi og Molekylær Biologi, Danmark.
authors.forename: G
authors.initials: G
authors.lastname: Oliviero
authors.affiliation: UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Cagney
authors.affiliation: UCD Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland.|UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: Crean