RT Journal Article
T1 Telomere Length Defines the Cardiomyocyte Differentiation Potency of Mouse Induced Pluripotent Stem Cells
A1 Aguado Sánchez, Tania
A1 Gutiérrez, Francisco J.
A1 Aix, Esther
A1 Schneider, Ralph P.
A1 Giovinazzo, Giovanna
A1 Blasco, María A.
A1 Flores, Ignacio
AB Induced pluripotent stem cells (iPSCs) can be differentiated in vitro and in vivo to all cardiovascular lineages and are therefore a promising cell source for cardiac regenerative therapy. However, iPSC lines do not all differentiate into cardiomyocytes (CMs) with the same efficiency. Here, we show that telomerase-competent iPSCs with relatively long telomeres and high expression of the shelterin-complex protein TRF1 (iPSChighT) differentiate sooner and more efficiently into CMs than those with relatively short telomeres and low TRF1 expression (iPSClowT). Ascorbic acid, an enhancer of cardiomyocyte differentiation, further increases the cardiomyocyte yield from iPSChighT but does not rescue the cardiomyogenic potential of iPSClowT. Interestingly, although iPSCslowT differentiate very poorly to the mesoderm and endoderm lineages, they differentiate very efficiently to the ectoderm lineage, indicating that cell fate can be determined by in vitro selection of iPSCs with different telomere content. Our findings highlight the importance of selecting iPSCs with ample telomere reserves in order to generate high numbers of CMs in a fast, reliable, and efficient way.
PB Oxford University Press
SN 1066-5099
YR 2016
FD 2016-09-26
LK https://hdl.handle.net/20.500.14352/91532
UL https://hdl.handle.net/20.500.14352/91532
LA eng
NO Ministerio de Economía, Industria y Competitividad (MINECO)
NO Fundación Pro-CNIC
NO Centro de Excelencia Severo Ochoa
NO Consejo Europeo de Investigación (ERC)
NO Comunidad de Madrid
NO Fundación Botín
NO Fondo de Investigación AXA
NO Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares
NO Ministerio de Educación
NO Asociación Española Contra el Cáncer (AECC)
DS Docta Complutense
RD 1 sept 2024