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Artículo

OCT4 expression mediates partial cardiomyocyte reprogramming of mesenchymal stromal cells

Yannarelli, Gustavo GabrielIcon ; Pacienza, Natalia AlejandraIcon ; Montanari, Sonia; Santa Cruz, Diego MarioIcon ; Viswanathan, Sowmya; Keating, Armand
Fecha de publicación: 12/2017
Editorial: Public Library of Science
Revista: Plos One
ISSN: 1932-6203
Idioma: Inglés
Tipo de recurso: Artículo publicado

Resumen

Mesenchymal stem/stromal cells (MSCs) are in numerous cell therapy clinical trials, including for injured myocardium. Acquisition of cardiomyocyte characteristics by MSCs may improve cardiac regeneration but the mechanisms regulating this process are unclear. Here, we investigated whether the pluripotency transcription factor OCT4 is involved in the activation of cardiac lineage genetic programs in MSCs. We employed our established co-culture model of MSCs with rat embryonic cardiomyocytes showing co-expression of cardiac markers on MSCs independent of cell fusion. Bone marrow-derived MSCs were isolated from transgenic mice expressing GFP under the control of the cardiac-specific α-myosin heavy chain promoter. After 5 days of co-culture, MSCs expressed cardiac specific genes, including Nkx2.5, atrial natriuretic factor and α-cardiac actin. The frequency of GFP+ cells was 7.6±1.9%, however, these cells retained the stromal cell phenotype, indicating, as expected, only partial differentiation. Global OCT4 expression increased 2.6±0.7-fold in cocultured MSCs and of interest, 87±5% vs 79±4% of MSCs expressed OCT4 by flow cytometry in controls and after co-culture, respectively. Consistent with the latter observation, the GFP+ cells did not express nuclear OCT4 and showed a significant increase in OCT4 promoter methylation compared with undifferentiated MSCs (92% vs 45%), inferring that OCT4 is regulated by an epigenetic mechanism. We further showed that siRNA silencing of OCT4 in MSCs resulted in a reduced frequency of GFP+ cells in co-culture to less than 1%. Our data infer that OCT4 expression may have a direct effect on partial cardiomyocyte reprogramming of MSCs and suggest a new mechanism(s) associated with MSC multipotency and a requirement for crosstalk with the cardiac microenvironment.
Palabras clave: Mesenchymal Stromal Cells , Cardiac Regeneration , Oct4 , Epigenetic
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
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URI: http://hdl.handle.net/11336/48811
DOI: https://dx.doi.org/10.1371/journal.pone.0189131
URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189131
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Articulos(OCA HOUSSAY) [1813]
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Yannarelli, Gustavo Gabriel; Pacienza, Natalia Alejandra; Montanari, Sonia; Santa Cruz, Diego Mario; Viswanathan, Sowmya; et al.; OCT4 expression mediates partial cardiomyocyte reprogramming of mesenchymal stromal cells; Public Library of Science; Plos One; 12; 12; 12-2017; 1-20
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