Opposing effects of the basic helix-loop-helix transcription factor SCL on erythroid and monocytic differentiation.

Opposing effects of the basic helix-loop-helix transcription factor SCL on erythroid and monocytic differentiation.
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碱性螺旋-环-螺旋转录因子 SCL 对红细胞和单核细胞分化的相反作用。

DOI:
10.1182/blood.v87.1.102.102
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发表时间:
1996
期刊:
影响因子:
20.3
通讯作者:
I. Kirsch
I. Kirsch
中科院分区:
医学1区
文献类型:
--
作者:
T. Hoang;E. Paradis;G. Brady;F. Billia;K. Nakahara;N. Iscove;I. Kirsch

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SCL基因(也称为Tal-1或TCL 5)被发现是因为它与儿童T细胞淋巴样白血病的染色体易位有关。SCL编码碱性螺旋-环-螺旋(bHLH)因子,可作为转录激活因子或抑制因子发挥作用。在成人中,SCL表达仅限于造血细胞和组织,但其在谱系定型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。SCL表达测定在原代造血细胞通过筛选的cDNA样品获得的逆转录-聚合酶链反应(RT-PCR)从单细胞在不同阶段的分化。SCL RNA表达最高的双能和承诺红细胞前体细胞和减少随后的成熟为原成红细胞和正常成红细胞。相比之下,SCL mRNA在粒细胞和单核细胞及其成熟后代的前体细胞中低至检测不到。红系或单核细胞分化的双能细胞系,TF-1,SCL mRNA水平在红系分化过程中保持升高,并下调与单核细胞分化后观察到相同的表达模式。因此,TF-1被选为一个模型,以调查SCL表达的这种不同的模式在两个谱系的功能意义。四个独立的克隆稳定转染SCL表达载体表现出增强的自发性和δ-氨基乙酰丙酸诱导的红系分化,通过血型糖蛋白表达和血红蛋白化测量,与SCL是红系分化的正调节剂的观点一致。此外,组成型SCL表达干扰单核细胞分化,如通过粘附细胞的产生和响应于TPA的Fc γ RII的表达所评估的。这些结果表明,SCL的下调可能是单核细胞分化所必需的。
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.
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发表时间: 1994
影响因子: 11.1
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DOI: --
发表时间: 1995
期刊: Blood
影响因子: 20.3
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DOI: --
发表时间: 1993-11
期刊: Oncogene
影响因子: 8
作者:
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DOI: 10.1073/pnas.89.14.6353
发表时间: 1992
影响因子: 11.1
作者:
Sposi,NM;Zon,LI;Carè,A;Valtieri,M;Testa,U;Gabbianelli,M;Mariani,G;Bottero,L;Mather,C;Orkin,SH
通讯作者: Orkin,SH
DOI: 10.1126/science.1372755
发表时间: 1992-03-27
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: KADESCH, T