Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels

Zack Z. Wang, Kenneth Cohen, Ying Shao, Pamela Mole, David Dombkowski, David T. Scadden

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)100-109
Number of pages10
JournalBlood
Volume103
Issue number1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Hemangioblasts
Eph Family Receptors
Blood vessels
Embryonic Stem Cells
Stem cells
Cardiac Myocytes
Blood Vessels
Cell Differentiation
Blood
Mesoderm
Genes
Cells
Growth Differentiation Factors
Tissue
Neural Plate
Pluripotent Stem Cells
Cell Adhesion
Cell Movement
Cues
Blood Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels. / Wang, Zack Z.; Cohen, Kenneth; Shao, Ying; Mole, Pamela; Dombkowski, David; Scadden, David T.

In: Blood, Vol. 103, No. 1, 01.01.2004, p. 100-109.

Research output: Contribution to journalArticle

Wang, Zack Z. ; Cohen, Kenneth ; Shao, Ying ; Mole, Pamela ; Dombkowski, David ; Scadden, David T. / Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels. In: Blood. 2004 ; Vol. 103, No. 1. pp. 100-109.
@article{95037707a14f411986f607dd8fd38632,
title = "Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels",
abstract = "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.",
author = "Wang, {Zack Z.} and Kenneth Cohen and Ying Shao and Pamela Mole and David Dombkowski and Scadden, {David T.}",
year = "2004",
month = "1",
day = "1",
doi = "10.1182/blood-2003-04-1063",
language = "English (US)",
volume = "103",
pages = "100--109",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

}

TY - JOUR

T1 - Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels

AU - Wang, Zack Z.

AU - Cohen, Kenneth

AU - Shao, Ying

AU - Mole, Pamela

AU - Dombkowski, David

AU - Scadden, David T.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0347597774&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0347597774&partnerID=8YFLogxK

U2 - 10.1182/blood-2003-04-1063

DO - 10.1182/blood-2003-04-1063

M3 - Article

C2 - 12958066

AN - SCOPUS:0347597774

VL - 103

SP - 100

EP - 109

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -