Hoang T, Paradis E, Brady G, Billia F, Nakahara K, Iscove N N, Kirsch I R
Clinical Research Institute of Montreal, Department of Pharmacology, University of Montreal, Canada.
Blood. 1996 Jan 1;87(1):102-11.
The SCL gene (also called Tal-1 or TCL5) was identified because of its association with chromosomal translocations in childhood T-cell lymphoid leukemias. SCL codes for a basic helix-loop-helix (bHLH) factor that can function as a transcriptional activator or repressor. In the adult, SCL expression is restricted to hematopoietic cells and tissues, but 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 hematopoietic cells through the screening of cDNA samples obtained by reverse transcription-polymerase chain reaction (RT-PCR) from single cells at 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 monocytes and their maturing progeny. The same pattern of expression was observed after erythroid or monocytic differentiation of a bipotent cell line, TF-1, in that SCL mRNA levels remained elevated during erythroid differentiation and were downregulated with monocytic differentiation. Accordingly, TF-1 was chosen as a model to investigate the functional 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-aminolevulinic 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, constitutive SCL expression interfered with monocytic differentiation, as assessed by the generation of adherent cells and the expression of Fc gamma RII in response to TPA. These results suggest that the downregulation of SCL may be required for monocytic differentiation.
SCL基因（也称为Tal-1或TCL5）因其与儿童T细胞淋巴白血病中的染色体易位有关而被鉴定出来。SCL编码一种碱性螺旋-环-螺旋（bHLH）因子，它可以作为转录激活剂或抑制剂发挥作用。在成年人中，SCL的表达仅限于造血细胞和组织，但其在谱系定向过程中的功能尚不清楚。本研究旨在探讨SCL在造血细胞分化中的作用。通过对从不同分化阶段的单细胞经逆转录-聚合酶链反应（RT-PCR）获得的cDNA样本进行筛选，确定原代造血细胞中SCL的表达情况。SCL RNA表达在双潜能和定向红细胞前体中最高，并随着随后向早幼红细胞和成红细胞的成熟而降低。相比之下，SCL mRNA在粒细胞和单核细胞前体及其成熟后代中很低或无法检测到。在双潜能细胞系TF-1进行红细胞或单核细胞分化后也观察到相同的表达模式，即SCL mRNA水平在红细胞分化过程中保持升高，而在单核细胞分化时被下调。因此，选择TF-1作为模型来研究SCL在这两个谱系中这种不同表达模式的功能意义。用SCL表达载体稳定转染的四个独立克隆表现出增强的自发和δ-氨基乙酰丙酸诱导的红细胞分化，这通过血型糖蛋白表达和血红蛋白化来衡量，这与SCL是红细胞分化的正调节因子的观点一致。此外，通过贴壁细胞的生成以及对佛波酯（TPA）反应中FcγRII的表达评估，组成型SCL表达干扰了单核细胞分化。这些结果表明，SCL的下调可能是单核细胞分化所必需的。
