Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels.
Differentiation of pluripotent embryonic stem (ES) cells is associated with expression of fate-specifying gene products. Coordinated development, however, must involve modifying factors that enable differentiation and growth to adjust in response to local microenvironmental determinants. We report here that the ephrin receptor, EphB4, known to be spatially restricted in expression and critical for organized vessel formation, modifies the rate and magnitude of ES cells acquiring genotypic and phenotypic characteristics of mesodermal tissues. Hemangioblast, blood cell, cardiomyocyte, and vascular differentiation was impaired in EphB4-/- ES cells in conjunction with decreased expression of mesoderm-associated, but not neuroectoderm-associated, genes. Therefore, EphB4 modulates the response to mesoderm induction signals. These data add differentiation kinetics to the known effects of ephrin receptors on mammalian cell migration and adhesion. We propose that modifying sensitivity to differentiation cues is a further means for ephrin receptors to contribute to tissue patterning and organization.
Wang
Zhengyu
Z
Centre of Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cohen
Kenneth
K
Shao
Ying
Y
Mole
Pamela
P
Dombkowski
David
D
Scadden
David T
DT
D000818:Animals; D001483:Base Sequence; D001773:Blood Cells / Q000166:cytology; D001808:Blood Vessels / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology*; D036224:Receptor, EphB4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D017931:DNA Primers; C086681:Ephb4 protein, mouse; D036224:Receptor, EphB4