ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages.
During hematopoiesis, myeloid progenitor cells give rise to granulocytes and macrophages. To study the role for ICSBP, a hematopoietic cell-specific transcription factor in myeloid cell development, the gene was introduced into myeloid progenitor cells established from ICSBP-/- mice. ICSBP retrovirus-transduced cells differentiated into mature macrophages with phagocytic activity, which coincided with the induction of specific target DNA binding activity. Similar to macrophages in vivo, ICSBP-transduced cells were growth arrested, expressed many macrophage-specific genes, and responded to macrophage activation signals. Contrary to this, ICSBP transducion led to repression of granulocyte-specific genes and inhibited G-CSF-mediated granulocytic differentiation in these and other myeloid progenitor cells. Together, ICSBP has a key role in the myeloid cell lineage selection and macrophage maturation.
Tamura
T
T
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nagamura-Inoue
T
T
Shmeltzer
Z
Z
Kuwata
T
T
Ozato
K
K
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D050835:Interferon Regulatory Factors; D007372:Interferons / Q000502:physiology; D019891:Leukopoiesis; D008264:Macrophages / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D012097:Repressor Proteins / Q000502:physiology*; D000099185:Interferon Regulatory Factor-8
D050835:Interferon Regulatory Factors; D007372:Interferons; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8