http://www.cnr.it/ontology/cnr/individuo/prodotto/ID224726
In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors (Articolo in rivista)
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- Label
- In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors (Articolo in rivista) (literal)
- Anno
- 2012-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1371/journal.pone.0051694 (literal)
- Alternative label
Vecellio Matteo1,2; Meraviglia Viviana2; Nanni Simona3; Barbuti Andrea4; Scavone Angela4; DiFrancesco Dario4; Farsetti Antonella5,6; Giulio Pompilio1,2;Colombo Gualtiero I.7;Capogrossi Maurizio C.8; Gaetano Carlo9; Rossini Alessandra1 (2012)
In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors
in PloS one
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Vecellio Matteo1,2; Meraviglia Viviana2; Nanni Simona3; Barbuti Andrea4; Scavone Angela4; DiFrancesco Dario4; Farsetti Antonella5,6; Giulio Pompilio1,2;Colombo Gualtiero I.7;Capogrossi Maurizio C.8; Gaetano Carlo9; Rossini Alessandra1 (literal)
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- 1 Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milano, Italy.
2 Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino, IRCCS, Milano, Italy.
3 Istituto di Patologia Medica, Università Cattolica del Sacro Cuore, Roma, Italy.
4 Dipartimento di Bioscienze, The PaceLab, Università di Milano, Milano, Italy.
5 Istituto Nazionale Tumori Regina Elena, Roma, Italy.
6 Istituto di Neurobiologia e Medicina Molecolare, Consiglio Nazionale delle Ricerche (CNR), Roma, Italy(*)
7 Laboratorio di Immunologia e Genomica Funzionale, Centro Cardiologico Monzino, IRCCS, Milano, Italy
8 Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata - IRCCS, Roma, Italy
9 Division of Cardiovascular Epigenetics, Department of Cardiology, Goethe University, Frankfurt am Main, Germany.
(*) Soppresso e confluito in IBCN (provv. n. 116 del 21/12/2010 prot. n. 91899) (literal)
- Titolo
- In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors (literal)
- Abstract
- Adult human cardiac mesenchymal-like stromal cells (CStC) represent a relatively accessible cell type useful for therapy. In this light, their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. The aim of the present work was to reprogram CStC into functionally competent cardiovascular precursors using epigenetically active small molecules. CStC were exposed to low serum (5% FBS) in the presence of 5 µM all-trans Retinoic Acid (ATRA), 5 µM Phenyl Butyrate (PB), and 200 µM diethylenetriamine/nitric oxide (DETA/NO), to create a novel epigenetically active cocktail (EpiC). Upon treatment the expression of markers typical of cardiac resident stem cells such as c-Kit and MDR-1 were up-regulated, together with the expression of a number of cardiovascular-associated genes including KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, and ?-MHC. In addition, profiling analysis revealed that a significant number of microRNA involved in cardiomyocyte biology and cell differentiation/proliferation, including miR 133a, 210 and 34a, were up-regulated. Remarkably, almost 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and, to a lower extent in a few cells, also the pacemaker I(f) current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern compatible with reduced proliferation and chromatin relaxation. Consistently, ChIP experiments performed with H3K4me3 or H3s10P histone modifications revealed the presence of a specific EpiC-dependent pattern in c-Kit, MDR-1, and Nkx2.5 promoter regions, possibly contributing to their modified expression. Taken together, these data indicate that CStC may be epigenetically reprogrammed to acquire molecular and biological properties associated with competent cardiovascular precursors. (literal)
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