Tel/PDGFRbeta inhibits self-renewal and directs myelomonocytic differentiation of ES cells.
The leukemic oncogene Tel/PDGFRbeta, was inducibly expressed in embryonic stem (ES) cells and the phenotypic and molecular changes occurring during hematopoietic differentiation investigated. Expression of Tel/PDGFRbeta resulted in an inability of ES cells to self-renew and caused a significant increase in myelopoiesis with a corresponding decrease in erythropoiesis. Analysis of gene expression patterns indicated a dramatic alteration in the levels of genes associated with self-renewal and differentiation, especially myelomonocytic genes in Tel/PDGFRbeta-expressing cells. This study indicates Tel/PDGFRbeta drives myelopoiesis by altering expression of genes involved in hematopoiesis and demonstrates the potential of this stem cell system to study oncogene-induced pathogenesis.
Dobbin
E
E
Biomedical Sciences Research Institute, University of Ulster, Cromore Road, Coleraine, Northern Ireland, UK.
Corrigan
P M
PM
Walsh
C P
CP
Welham
M J
MJ
Freeburn
R W
RW
Wheadon
H
H
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology; D038042:Myelopoiesis; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*
D053605:Leukemia Inhibitory Factor; D015514:Oncogene Proteins, Fusion; C120888:TEL-PDGFRbeta fusion protein, human