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  EXPRESSION OF A C-FMS(CSF-1R)-EGFP TRANSGENE IN GRANULOCYTES AND MACROPHAGES REFLECTS CLOSELY-RELATED TRANSCRIPTIONAL PROFILES AND IMPLIES TRANSLATIONAL CONTROL OF LINEAGE DIVERGENCE.

R. Tedjo Sasmono, Stephen L. Cronau, Timothy Ravasi, Rangi Kandane, Michael J. Hickey, Andrew D. Cook, S. Roy Himes, John A. Hamilton and David A. Hume.



Status: Submitted

Abstract: The differentiation of macrophages from their progenitors is controlled by macrophage colony-stimulating factor (CSF-1), which binds to a receptor encoded by the c-fms proto-oncogene. We have previously used the promoter region of c-fms to direct expression of an EGFP reporter gene to resident macrophage populations in transgenic mice. In this paper, we show that the EGFP reporter is also expressed in all granulocytes detected either with the Gr-1 antibody, which binds to both Ly-6C and Ly-6G, or with a Ly-6G-specific antibody. We show that transgene expression reflects the presence of c-fms mRNA; however, the mRNA is not translated into CSF-1R protein in granulocytes. The same pattern is observed with the macrophage-specific F4/80 marker. Based upon these findings, we performed comparative array profiling of highly-purified granulocytes and macrophages. The patterns of mRNA expression were overwhelmingly similar, and differ predominantly through granulocyte-specific expression of a small subset of transcription factors (Egr1, HoxB7, STAT3) and known abundant granulocyte proteins (S100A8, S100A9, neutrophil elastase etc). These findings suggest that translation control is an important determinant of granulocyte function, and that appropriate stimuli might mediate rapid interconversion of the major myeloid cell types, for example, in inflammation.

Keywords: Macrophages; Neutrophils; CSF-1R; myeloid-specific genes
 
   
 Files :
Gene expression values comparison between granulocyte and macrophages - 4830 Kb
Raw data of the expression of all genes - 5634 Kb
Proportion of genes expressed in Granulocytes, Macrophages, or Both - 68 Kb