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IL-3 Induces Inhibitor of DNA-Binding Protein-1 in Hemopoietic Progenitor Cells and Promotes Myeloid Cell Development¹

Wilairat Leeanansaksiri^2,*, Hui Wang^2,*,, John M. Gooya^*, Katie Renn^*, Mehrnoosh Abshari^*, Schickwann Tsai and Jonathan R. Keller^3,*

^* Basic Research Program, Science Applications International Corporation (SAIC)-Frederick and Laboratory of Molecular Immunoregulation and Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702; and Division of Hematology, School of Medicine, University of Utah, Salt Lake City, UT 84132

Hemopoiesis depends on the expression and regulation of transcription factors, which control the maturation of specific cell lineages. We found that the helix-loop-helix transcription factor inhibitor of DNA-binding protein 1 (Id1) is not expressed in hemopoietic stem cells (HSC), but is increased in more committed myeloid progenitors. Id1 levels decrease during neutrophil differentiation, but remain high in differentiated macrophages. Id1 is expressed at low levels or is absent in developing lymphoid or erythroid cells. Id1 expression can be induced by IL-3 in HSC during myeloid differentiation, but not by growth factors that promote erythroid and B cell development. HSC were transduced with retroviral vectors that express Id1 and were transplanted in vivo to evaluate their developmental potential. Overexpression of Id1 in HSC promotes myeloid but impairs B and erythroid cell development. Enforced expression of Id1 in committed myeloid progenitor cells inhibits granulocyte but not macrophage differentiation. Therefore, Id1 may be part of the mechanism regulating myeloid vs lymphoid/erythroid cell fates, and macrophage vs neutrophil maturation.

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