EXPRESSION OF BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS IN EXPLANTHEMATOPOIETIC PROGENITORS

The basic helix-loop-helix (bHLH) transcription factors form heterodim ers and control steps in cellular differentiation. We have studied fou r bHLH transcription factors, SCL, lyl-1, E12/E47, and Id-1, in indivi dual lineage-defined progenitors and hematopoietic growth factor-depen dent cell lines, evaluating mRNA expression and the effects of growth factors and cell cycle phase on this expression. Single lineage-define d progenitors selected from early murine colony starts and grown under permissive conditions were analyzed by RT-PCR. SCL and E12/E47 were e xpressed in the vast majority of tri-, bi-, and unilineage progenitors of erythroid, macrophage, megakaryocyte, and neutrophil lineages. Exp ression for E12/E47 was not seen in unilineage megakaryocyte and eryth roid or bilineage neutrophil/mast cell progenitors. Lyl-1 showed a mor e restricted pattern of expression, although expression was seen in so me bi- and unilineage progenitors. No expression was detected in eryth roid, erythroid-megakaryocyte-macrophage, macrophage-neutrophil, macro phage, or megakaryocytic progenitors. Id-1, an inhibitory bHLH transcr iption factor, was also widely expressed in all bi- and unilineage pro genitors; only the trilineage erythroid-megakaryocyte-macrophage proge nitors failed to show expression. Expression of these factors within a progenitor class was generally heterogeneous, with some progenitors s howing expression and some not. This was seen even when two sister cel ls from the same colony start were analyzed. Id-1, but not E12/E47, mR NA was increased in FDC-P1 and MO7E hematopoietic cell lines after exp osure 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 ce lls. These results suggest that SCL, lyl-1, E12/E47, and Id-1 are impo rtant in hematopoietic progenitor cell regulation, and that their expr ession in hematopoietic cells varies in response to cytokines and/or d uring transit through cell cycle. (C) 1996 Wiley-Liss, Inc.