Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells

Zhengyu Wang, Nobuyuki Miura, Andres Bonelli, Pamela Mole, Nadia Carlesso, Douglas P. Olson, David T. Scadden

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

EphB4 (HTK) and its ligand, ephrinB2, are critical for angiogenesis and result in fatal abnormalities of capillary formation in null mice. EphB4 was originally identified in human bone marrow CD34+ cells by us and has since been reported to be expressed in erythroid progenitors, whereas the ligand ephrinB2 is expressed in bone marrow stromal cells. Reasoning that the developmental relationship between angiogenesis and hematopoiesis implies common regulatory molecules, we assessed whether EphB4 signaling influences the function and phenotype of primitive human hematopoietic cells. Ectopically expressed EphB4 in cell lines of restricted differentiation potential promoted megakaryocytic differentiation, but not granulocytic or monocytic differentiation. Primary cord blood CD34+ cells transduced with EphB4 resulted in the elevated expression of megakaryocytic and erythroid specific markers, consistent with EphB4 selectively enhancing some lineage-committed progenitors. In less mature cells, EphB4 depleted primitive cells, as measured by long-term culture-initiating cells or CD34+CD38- cell numbers, and increased progenitor cells of multiple cell types. Effects of ectopic EphB4 expression could be abrogated by either targeted mutations of select tyrosine residues or by the tyrosine kinase inhibitor, genistein. These data indicate that EphB4 accelerates the differentiation of primitive cells in a nonlineage-restricted manner but alters only select progenitor populations, influencing lineages linked by common ancestry with endothelial cells. EphB4 enforces preferential megakaryocytic and erythroid differentiation and may be a molecular bridge between angiogenesis and hematopoiesis.

Original languageEnglish (US)
Pages (from-to)2740-2747
Number of pages8
JournalBlood
Volume99
Issue number8
DOIs
StatePublished - Apr 15 2002
Externally publishedYes

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Receptor Protein-Tyrosine Kinases
Bone
Cells
Ligands
Genistein
Endothelial cells
Hematopoiesis
Cell culture
Protein-Tyrosine Kinases
Tyrosine
Blood
Molecules
Mesenchymal Stromal Cells
Fetal Blood
Bone Marrow Cells
Cell Differentiation
Blood Cells
Stem Cells
Endothelial Cells
Cell Culture Techniques

ASJC Scopus subject areas

  • Hematology

Cite this

Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. / Wang, Zhengyu; Miura, Nobuyuki; Bonelli, Andres; Mole, Pamela; Carlesso, Nadia; Olson, Douglas P.; Scadden, David T.

In: Blood, Vol. 99, No. 8, 15.04.2002, p. 2740-2747.

Research output: Contribution to journalArticle

Wang, Z, Miura, N, Bonelli, A, Mole, P, Carlesso, N, Olson, DP & Scadden, DT 2002, 'Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells', Blood, vol. 99, no. 8, pp. 2740-2747. https://doi.org/10.1182/blood.V99.8.2740
Wang, Zhengyu ; Miura, Nobuyuki ; Bonelli, Andres ; Mole, Pamela ; Carlesso, Nadia ; Olson, Douglas P. ; Scadden, David T. / Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. In: Blood. 2002 ; Vol. 99, No. 8. pp. 2740-2747.
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