Open AccessTelomere Length Defines the Cardiomyocyte Differentiation Potency of Mouse Induced Pluripotent Stem Cells
Author(s) -
Aguado Tania,
Gutiérrez Francisco J.,
Aix Esther,
Schneider Ralph P.,
Giovinazzo Giovanna,
Blasco María A.,
Flores Ignacio
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2497
Subject(s) - biology , induced pluripotent stem cell , telomere , telomerase , endoderm , microbiology and biotechnology , cellular differentiation , stem cell , ectoderm , regenerative medicine , shelterin , reprogramming , embryonic stem cell , directed differentiation , genetics , cell , embryo , dna , gene , transcription factor , embryogenesis , dna binding protein
A bstract 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 (iPSC highT ) differentiate sooner and more efficiently into CMs than those with relatively short telomeres and low TRF1 expression (iPSC lowT ). Ascorbic acid, an enhancer of cardiomyocyte differentiation, further increases the cardiomyocyte yield from iPSC highT but does not rescue the cardiomyogenic potential of iPSC lowT . Interestingly, although iPSCs lowT 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. S tem C ells 2017;35:362–373