Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
Top Cited Papers
- 23 April 2008
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 453 (7194), 524-528
- https://doi.org/10.1038/nature06894
Abstract
The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1+ (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages1. To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDRlow/C-KIT(CD117)neg population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDRlow/C-KITneg cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDRlow/C-KITneg fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.Keywords
This publication has 26 references indexed in Scilit:
- Identification and targeting of the ROSA26 locus in human embryonic stem cellsNature Biotechnology, 2007
- Human embryonic stem cell transplantation to repair the infarcted myocardiumHeart, 2007
- ES cells for troubled hearts.Nature Biotechnology, 2007
- Human cardiac stem cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- 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
- Developmental Origin of a Bipotential Myocardial and Smooth Muscle Cell Precursor in the Mammalian HeartCell, 2006
- Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation culturesBlood, 2006
- Micro-Electrode Arrays in Cardiac Safety PharmacologyDrug Safety, 2004
- Isl1 Identifies a Cardiac Progenitor Population that Proliferates Prior to Differentiation and Contributes a Majority of Cells to the HeartDevelopmental Cell, 2003
- Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse.Genes & Development, 1995