PU.1 supports proliferation of immature erythroid progenitors.
Despite normal levels of erythropoiesis in PU.1(-/-) embryos, PU.1(-/-) fetal hematopoietic progenitors are unable to establish sustained erythropoiesis in the adult bone marrow. This study demonstrates that PU.1(-/-) fetal erythroid progenitors are synergistically expanded by TPO plus SCF, but not combinations of EPO plus SCF, IL-3 or GM-CSF. The EPO defect is not corrected by a constitutively active variant of EPOR. Microarray analysis identified several candidate PU.1 target genes known to affect cytokine signaling and gene regulation in the erythroid lineage. These data suggest that PU.1 plays an important role in regulating the proliferation of immature erythroid progenitors.
Fisher
Robert C
RC
Program in Stem Cell Biology and Regenerative Medicine, Shands Cancer Center, Department of Molecular Genetics and Microbiology, Box 100232, Room R4-293, University of Florida, Gainesville, FL 32610, USA. rbfisher@ufl.edu
Slayton
William B
WB
Chien
Christopher
C
Guthrie
Steven M
SM
Bray
Christopher
C
Scott
Edward W
EW
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000378:metabolism*; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007377:Interleukin-3 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins; D020411:Oligonucleotide Array Sequence Analysis; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D017467:Receptors, Erythropoietin; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor; D019089:Stem Cell Factor / Q000378:metabolism; D013926:Thrombopoietin / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D015415:Biomarkers; D004268:DNA-Binding Proteins; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D007377:Interleukin-3; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008894:Milk Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D019089:Stem Cell Factor; D013926:Thrombopoietin; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C509248:Ptpn6 protein, mouse