Insulin-Like Growth Factor Promotes Cardiac Lineage Induction In Vitro by Selective Expansion of Early Mesoderm
Open Access
- 4 February 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 32 (6), 1493-1502
- https://doi.org/10.1002/stem.1660
Abstract
A thorough understanding of the developmental signals that direct pluripotent stem cells (PSCs) toward a cardiac fate is essential for translational applications in disease modeling and therapy. We screened a panel of 44 cytokines/signaling molecules for their ability to enhance Nkx2.5+ cardiac progenitor cell (CPC) formation during in vitro embryonic stem cell (ESC) differentiation. Treatment of murine ESCs with insulin or insulin-like growth factors (IGF1/2) during early differentiation increased mesodermal cell proliferation and, consequently, CPC formation. Furthermore, we show that downstream mediators of IGF signaling (e.g., phospho-Akt and mTOR) are required for this effect. These data support a novel role for IGF family ligands to expand the developing mesoderm and promote cardiac differentiation. Insulin or IGF treatment could provide an effective strategy to increase the PSC-based generation of CPCs and cardiomyocytes for applications in regenerative medicine. Stem Cells 2014;32:1493–1502Keywords
This publication has 39 references indexed in Scilit:
- Single‐Cell Phospho‐Protein Analysis by Flow CytometryCurrent Protocols in Immunology, 2012
- Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct ReprogrammingCell Stem Cell, 2012
- Wnt Signaling Exerts an Antiproliferative Effect on Adult Cardiac Progenitor Cells Through IGFBP3Circulation Research, 2011
- Regulation of Insulin-Like Growth Factor Signaling by Yap Governs Cardiomyocyte Proliferation and Embryonic Heart SizeScience Signaling, 2011
- Small-Molecule Inhibitors of the Wnt Pathway Potently Promote Cardiomyocytes From Human Embryonic Stem Cell–Derived MesodermCirculation Research, 2011
- Harnessing the potential of induced pluripotent stem cells for regenerative medicineNature, 2011
- Role of Mesodermal FGF8 and FGF10 Overlaps in the Development of the Arterial Pole of the Heart and Pharyngeal Arch ArteriesCirculation Research, 2010
- Biphasic role for Wnt/β-catenin signaling in cardiac specification in zebrafish and embryonic stem cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006
- Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditionsProceedings of the National Academy of Sciences of the United States of America, 2006