PU.1 supports proliferation of immature erythroid progenitors

Leuk Res. 2004 Jan;28(1):83-9. doi: 10.1016/s0145-2126(03)00178-4.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Cell Division
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / immunology
  • Embryo, Mammalian / metabolism
  • Erythroid Precursor Cells / cytology*
  • Erythroid Precursor Cells / immunology
  • Erythroid Precursor Cells / metabolism
  • Erythropoiesis / physiology*
  • Erythropoietin / metabolism*
  • Gene Expression Profiling
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Green Fluorescent Proteins
  • Interleukin-3 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Milk Proteins*
  • Oligonucleotide Array Sequence Analysis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptors, Erythropoietin
  • Recombinant Fusion Proteins / metabolism
  • STAT5 Transcription Factor
  • Stem Cell Factor / metabolism
  • Thrombopoietin / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Interleukin-3
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • Milk Proteins
  • Proto-Oncogene Proteins
  • Receptors, Erythropoietin
  • Recombinant Fusion Proteins
  • STAT5 Transcription Factor
  • Stem Cell Factor
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • Erythropoietin
  • Green Fluorescent Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Thrombopoietin
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn6 protein, mouse