OPPOSING EFFECTS OF THE BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR SCL ON ERYTHROID AND MONOCYTIC DIFFERENTIATION

The SCL gene (also called Tal-1 or TCL5) was identified because of its association with chromosomal translocations in childhood T-cell lymph oid leukemias. SCL codes for a basic helix-loop-helix (bHLH) factor th at can function as a transcriptional activator or repressor. In the ad ult, SCL expression is restricted to hematopoietic cells and tissues, hut its function in the process of lineage commitment is unknown. The present study was designed to address the role of SCL in hematopoietic cell differentiation. SCL expression was determined in primary hemato poietic cells through the screening of cDNA samples obtained by revers e transcription-polymerase chain reaction (RT-PCR) from single cells a t different stages of differentiation. SCL RNA expression was highest in bipotential and committed erythroid precursors and diminished with subsequent maturation to proerythroblasts and normoblasts. In contrast , SCL mRNA was low to undetectable in precursors of granulocytes and m onocytes and their maturing progeny. The same pattern of expression wa s observed after erythroid or monocytic differentiation of a bipotent cell line, TF-1, in that SCL mRNA levels remained elevated during eryt hroid differentiation and were downregulated with monocytic differenti ation. Accordingly, TF-1 was chosen as a model to investigate the func tional significance of this divergent pattern of SCL expression in the two lineages. four independent clones stably transfected with an SCL expression vector exhibited enhanced spontaneous and delta-aminolevuli nic acid-induced erythroid differentiation as measured by glycophorin expression and hemoglobinization, consistent with the view that SCL is a positive regulator of erythroid differentiation. Furthermore, const itutive SCL expression interfered with monocytic differentiation, as a ssessed by the generation of adherent cells and the expression of Fc g amma RII in response to TPA. These results suggest that the downregula tion of SCL may be required for monocytic differentiation. (C) 1996 by The American Society of Hematology.