CCAAT enhancer binding protein α is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors
CCAAT enhancer binding protein α is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors
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DOI：
10.1128/mcb.18.7.4301
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发表时间：
1998-07-01
影响因子：
5.3
通讯作者：
Tenen, DG
中科院分区：
文献类型：
--
作者：
Radomska, HS;Huettner, CS;Tenen, DG
转录因子CCAAT/增强子结合蛋白或（C/EBP α）调节许多骨髓细胞特异性基因。为了阐明C/EBP α在人粒系形成中的作用，我们研究了其在人原代细胞和双能（粒细胞/单核细胞）骨髓细胞系中的表达和功能。我们发现，C/EBP α的表达开始与承诺的多潜能前体的髓系，是特别上调粒细胞分化过程中，并迅速下调在替代单核细胞途径。在稳定转染的双能细胞中单独的C/EBP α的条件表达触发嗜中性细胞分化，伴随着粒细胞特异性粒细胞集落刺激因子受体和次级颗粒蛋白基因的上调。此外，诱导表达的C/EBP α在双能前体阻断他们的单核细胞分化程序。这些结果表明，C/EBP α作为骨髓分化开关作用于双能前体细胞，并指导它们成熟为粒细胞。
The transcription factor CCAAT/enhancer binding protein or (C/EBP alpha) regulates a number of myeloid cell-specific genes. To delineate the role of C/EBP alpha in human granulopoiesis,,ve studied its expression and function in human primary cells and bipotential (granulocytic/monocytic) myeloid cell lines. We show that the expression of C/EBP alpha initiates with the commitment of multipotential precursors to the myeloid lineage, is specifically upregulated during granulocytic differentiation, and is rapidly downregulated during the alternative monocytic pathway. Conditional expression of C/EBP alpha alone in stably transfected bipotential cells triggers neutrophilic differentiation, concomitant with upregulation of the granulocyte-specific granulocyte colony-stimulating factor receptor and secondary granule protein genes. Moreover, induced expression of C/EBP alpha in bipotential precursors blocks their monocytic differentiation program. These results indicate that C/EBP alpha serves as a myeloid differentiation switch acting on bipotential precursors and directing them to mature to granulocytes.