Nitric Oxide determines mesodermic differentiation of mouse embryonic stem cells by activating class IIa histone deacetylases: potential therapeutic implications in a mouse model of hindlimb ischemia (Articolo in rivista)

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  • Nitric Oxide determines mesodermic differentiation of mouse embryonic stem cells by activating class IIa histone deacetylases: potential therapeutic implications in a mouse model of hindlimb ischemia (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Spallotta F.1, Diana Rosati J.1, Straino S.1, Nanni S.2, Grasselli A.3,4, Ambrosino V.1, Rotili D.5, Valente S.5, Farsetti A.3, Mai A.5, Capogrossi M.C.1, Gaetano C.1, Illi B.6 (2010)
    Nitric Oxide determines mesodermic differentiation of mouse embryonic stem cells by activating class IIa histone deacetylases: potential therapeutic implications in a mouse model of hindlimb ischemia
    in Stem cells (Dayt. Ohio)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Spallotta F.1, Diana Rosati J.1, Straino S.1, Nanni S.2, Grasselli A.3,4, Ambrosino V.1, Rotili D.5, Valente S.5, Farsetti A.3, Mai A.5, Capogrossi M.C.1, Gaetano C.1, Illi B.6 (literal)
Pagina inizio
  • 431 (literal)
Pagina fine
  • 442 (literal)
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  • 28 (literal)
Rivista
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  • 2010 Jan 13. [Epub ahead of print] IF= 7.741 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1Laboratorio di Patologia Vascolare, Istituto Dermopatico dell' Immacolata - IRCCS, Rome, ITALY 2Istituto di Patologia Medica, Università Cattolica del Sacro Cuore, Rome, ITALY 3Istituto di Neurobiologia e Medicina Molecolare, CNR, Rome ITALY 4Istituto Nazionale Ricovero e Cura Anziani - IRCCS, Ancona, ITALY 5Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento Studi Farmaceutici Università degli Studi di Roma La Sapienza, Rome, ITALY 6Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino - IRCCS, Milan, ITALY (literal)
Titolo
  • Nitric Oxide determines mesodermic differentiation of mouse embryonic stem cells by activating class IIa histone deacetylases: potential therapeutic implications in a mouse model of hindlimb ischemia (literal)
Abstract
  • In human endothelial cells Nitric Oxide (NO) results in class IIa Histone Deacetylases (HDACs) activation and marked histone deacetylation. It is unknown whether similar epigenetic events occur in embryonic stem cells (ES) exposed to NO and how this treatment could influence ES therapeutic potential during tissue regeneration. The present study reports that the NO-dependent class IIa HDACs sub-cellular localization and activity decreases the global acetylation level of H3 histones in ES and that this phenomenon is associated to the inhibition of Oct4, Nanog and KLF4 expression. Further, a NO-induced formation of macromolecular complexes including HDAC3, 4, 7 and protein phosphatase 2A (PP2A) have been detected. These process correlated with the expression of the mesodermal specific protein Brachyury (Bry) and the appearance of several vascular and skeletal muscle differentiation markers. These events were abolished by the class IIa-specific inhibitor MC1568 and by HDAC4 or HDAC7 short interfering RNA (siRNA). NO ability to induce mesodermic/cardiovascular gene expression prompted us to evaluate the regenerative potential of these cells in a mouse model of hindlimb ischemia. We found that NO-treated ES injected into the cardiac left ventricle selectively localized in the ischemic hindlimb and contributed to the regeneration of muscular and vascular structures. These findings establish a key role for NO and class IIa HDACs modulation in ES mesodermal commitment and enhanced regenerative potential in vivo. (literal)
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