title: In vitro modeling of paraxial and lateral mesoderm differentiation reveals early reversibility.
abstract: Endothelial cells (ECs) are thought to be derived mainly from the vascular endothelial growth factor receptor 2 (VEGFR-2)+ lateral mesoderm during early embryogenesis. In this study, we specified several pathways for EC differentiation using a murine embryonic stem (ES) cell differentiation culture system that is a model for cellular processes during early embryogenesis. Based on the results of in vitro fate analysis, we show that, in the main pathway, committed ECs are differentiated through the VEGFR-2+ platelet-derived growth factor receptor alpha (PDGFR-alpha)- single-positive (VSP) population that is derived from the VEGFR-2+ PDGFR-alpha+ double-positive (DP) population. This major differentiation course was also confirmed using DNA microarray analysis. In addition to this main pathway, however, ECs also can be generated from the VEGFR-2- PDGFR-alpha+ single-positive (PSP) population, which represents the paraxial mesodermal lineage and is also derived from the DP population. Our results strongly suggest that, even after differentiation from the common progenitor DP population into the VSP and PSP populations, these two populations continue spontaneous switching of their surface phenotype, which results in switching of their eventual fates. The rate of this interlineage conversion between VSP and PSP is unexpectedly high. Because of this potential to undergo fate switch, we conclude that ECs can be generated via multiple pathways in in vitro ES cell differentiation.
authors.affiliation: Laboratory for Stem Cell Biology, RIKEN Center for Development Biology, 2-2-3 Minatojimaminamimachi, Chuo-ku, Kobe, 650-0047, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sakurai
authors.forename: Takumi
authors.initials: T
authors.lastname: Era
authors.forename: Lars Martin
authors.initials: LM
authors.lastname: Jakt
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nakai
authors.forename: Satomi
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000172:deficiency / Q000378:metabolism
chemical_list: D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2