Abstract
The requirement of the transcription factor PU.1 for macrophage development has been well documented. However, the target genes regulated by PU.1 controlling macrophage maturation are not known. A granulocyte macrophage colony stimulating factor (GM-CSF)-dependent PU.1 null monocytic precursor cell was stably transduced with a PU.1-expressing retrovirus. The expression of PU.1 altered the surface expression of a few proteins expressed on monocytes; these cells, however, remained GM-CSF dependent and maintained an immature phenotype. In contrast to the PU.1 null cells, the cells expressing PU.1 responded to macrophage colony stimulating factor (M-CSF) with subsequent development into mature macrophages. Using suppressive subtractive hybridization between the PU.1 null and immature PU.1 rescued cells, three genes, MRP-14, Dap12 and CD53, were found expressed in the rescued cells, but not in the PU.1 null cells. In addition, these genes were modulated during M-CSF-induced maturation of the PU.1 rescued cells. The PU.1 null and rescued early monocytic cells provide a useful model to study the role of PU.1 in macrophage development.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antigens, CD / genetics*
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / genetics*
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Blotting, Northern
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Calgranulin B / metabolism*
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Cell Differentiation / genetics
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Gene Expression Regulation, Developmental* / drug effects
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Genetic Vectors
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Macrophage Colony-Stimulating Factor / pharmacology
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Membrane Proteins
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Monocytes / metabolism*
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Nucleic Acid Hybridization
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA / genetics
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RNA, Messenger / analysis
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Receptors, Immunologic / genetics*
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Receptors, Immunologic / metabolism
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Retroviridae / genetics
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Tetraspanin 25
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Trans-Activators / biosynthesis
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transduction, Genetic
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Up-Regulation
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD53 protein, human
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Calgranulin B
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Membrane Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Receptors, Immunologic
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TYROBP protein, human
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Tetraspanin 25
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Trans-Activators
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proto-oncogene protein Spi-1
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RNA
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Macrophage Colony-Stimulating Factor
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Granulocyte-Macrophage Colony-Stimulating Factor