Telomere Length Defines the Cardiomyocyte Differentiation Potency of Mouse Induced Pluripotent Stem Cells. 2017

Tania Aguado, and Francisco J Gutiérrez, and Esther Aix, and Ralph P Schneider, and Giovanna Giovinazzo, and María A Blasco, and Ignacio Flores
Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Madrid, Spain.

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. Stem Cells 2017;35:362-373.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001205 Ascorbic Acid A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Vitamin C,Ascorbic Acid, Monosodium Salt,Ferrous Ascorbate,Hybrin,L-Ascorbic Acid,Magnesium Ascorbate,Magnesium Ascorbicum,Magnesium di-L-Ascorbate,Magnorbin,Sodium Ascorbate,Acid, Ascorbic,Acid, L-Ascorbic,Ascorbate, Ferrous,Ascorbate, Magnesium,Ascorbate, Sodium,L Ascorbic Acid,Magnesium di L Ascorbate,di-L-Ascorbate, Magnesium
D048429 Cell Size The quantity of volume or surface area of CELLS. Cell Volume,Cell Sizes,Cell Volumes,Size, Cell,Sizes, Cell,Volume, Cell,Volumes, Cell
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057026 Induced Pluripotent Stem Cells Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS. Human Induced Pluripotent Stem Cell,IPS Cell,IPS Cells,Induced Pluripotent Stem Cell,Fibroblast-Derived IPS Cells,Fibroblast-Derived Induced Pluripotent Stem Cells,Human Induced Pluripotent Stem Cells,hiPSC,Cell, Fibroblast-Derived IPS,Cell, IPS,Cells, Fibroblast-Derived IPS,Cells, IPS,Fibroblast Derived IPS Cells,Fibroblast Derived Induced Pluripotent Stem Cells,Fibroblast-Derived IPS Cell,IPS Cell, Fibroblast-Derived,IPS Cells, Fibroblast-Derived
D058732 Embryoid Bodies Spontaneous aggregations of human embryonic stem cells that occur in vitro after culturing in a medium that lacks LEUKEMIC INHIBITORY FACTOR. The embryoid bodies can further differentiate into cells that represent different lineages. Bodies, Embryoid,Body, Embryoid,Embryoid Body
D059505 Telomere Homeostasis Maintenance of TELOMERE length. During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING.) Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends. Telomere Length Maintenance,Telomere Lengthening,Homeostasis, Telomere,Length Maintenance, Telomere,Lengthening, Telomere,Maintenance, Telomere Length

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