title: Increased cardiogenesis in P19-GFP teratocarcinoma cells expressing the propeptide IGF-1Ea.
abstract: The mechanism implicated in differentiation of endogenous cardiac stem cells into cardiomyocytes to regenerate the heart tissue upon an insult remains elusive, limiting the therapeutical goals to exogenous cell injection and/or gene therapy. We have shown previously that cardiac specific overexpression of the insulin-like growth factor 1 propeptide IGF-1Ea induces beneficial myocardial repair after infarct. Although the mechanism is still under investigation, the possibility that this propeptide may be involved in promoting stem cell differentiation into the cardiac lineage has yet to be explored. To investigate whether IGF-1Ea promote cardiogenesis, we initially modified P19 embryonal carcinoma cells to express IGF-1Ea. Taking advantage of their cardiomyogenic nature, we analyzed whether overexpression of this propeptide affected cardiac differentiation program. The data herein presented showed for the first time that constitutively overexpressed IGF-1Ea increased cardiogenic differentiation program in both undifferentiated and DMSO-differentiated cells. In details, IGF-1Ea overexpression promoted localization of alpha-actinin in finely organized sarcomeric structure compared to control cells and upregulated the cardiac mesodermal marker NKX-2.5 and the ventricular structural protein MLC2v. Furthermore, activated IGF-1 signaling promoted cardiac mesodermal induction in undifferentiated cells independently of cell proliferation. This analysis suggests that IGF-1Ea may be a good candidate to improve both in vitro production of cardiomyocytes from pluripotent stem cells and in vivo activation of the differentiation program of cardiac progenitor cells.
authors.affiliation: Heart Science Centre, National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Bhawana
authors.initials: B
authors.lastname: Poudel
authors.forename: Daniel
authors.initials: D
authors.lastname: Bilbao
authors.forename: Padmini
authors.initials: P
authors.lastname: Sarathchandra
authors.forename: Renee
authors.initials: R
authors.lastname: Germack
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Santini
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D006321:Heart / Q000196:embryology*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D008648:Mesoderm / Q000196:embryology; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*; D038081:Organogenesis; D010455:Peptides / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
chemical_list: D010455:Peptides; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D007334:Insulin-Like Growth Factor I; D017346:Protein Serine-Threonine Kinases
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