Expression of basic helix-loop-helix transcription factors in explant hematopoietic progenitors
Department of Cell Biology; Department of Pediatrics; Deparmtent of Medicine
Medical Subject Headings
Animals; Blotting, Northern; Cells, Cultured; *Gene Expression Regulation, Developmental; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; *Helix-Loop-Helix Motifs; Hematopoietic Stem Cells; Humans; Interleukin-3; Mice; Molecular Sequence Data; Polymerase Chain Reaction; RNA, Messenger; Time Factors; Transcription Factors; Tumor Cells, Cultured
The basic helix-loop-helix (bHLH) transcription factors form heterodimers and control steps in cellular differentiation. We have studied four bHLH transcription factors, SCL, lyl-1, E12/E47, and ld-1, in individual lineage-defined progenitors and hematopoietic growth factor-dependent cell lines, evaluating mRNA expression and the effects of growth factors and cell cycle phase on this expression. Single lineage-defined progenitors selected from early murine colony starts and grown under permissive conditions were analyzed by RT-PCR. SCL and E12/E47 were expressed in the vast majority of tri-, bi-, and unilineage progenitors of erythroid, macrophage, megakaryocyte, and neutrophil lineages. Expression for E12/E47 was not seen in unilineage megakaryocyte and erythroid or bilineage neutrophil/mast cell progenitors. Lyl-1 showed a more restricted pattern of expression, although expression was seen in some bi- and unilineage progenitors. No expression was detected in erythroid, erythroid-megakaryocyte-macrophage, macrophage-neutrophil, macrophage, or megakaryocytic progenitors. Id-1, an inhibitory bHLH transcription factor, was also widely expressed in all bi- and unilineage progenitors; only the trilineage erythroid-megakaryocyte-macrophage progenitors failed to show expression. Expression of these factors within a progenitor class was generally heterogeneous, with some progenitors showing expression and some not. This was seen even when two sister cells from the same colony start were analyzed. Id-1, but not E12/E47, mRNA was increased in FDC-P1 and MO7E hematopoietic cell lines after exposure to IL-3 or GM-CSF. Id-1, E12, and lyl-1 showed marked variation at different points in cell cycle in isoleucine-synchronized FDC-P1 cells. These results suggest that SCL, lyl-1, E12/E47, and Id-1 are important in hematopoietic progenitor cell regulation, and that their expression in hematopoietic cells varies in response to cytokines and/or during transit through cell cycle.
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Citation: J Cell Biochem. 1996 Jun 1;61(3):478-88. Link to article on publisher's site
Quesenberry, Peter J.; Iscove, Norman N.; Cooper, Cathleen L.; Brady, Gerard; Newburger, Peter E.; Stein, Gary S.; Stein, Janet L.; Reddy, G. Prem Veer; and Pearson-White, Sonia, "Expression of basic helix-loop-helix transcription factors in explant hematopoietic progenitors" (1996). Stein, Stein, Lian, vanWijnen Lab Publications. 76.