C/EBPα determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation
C/EBPα determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation
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DOI：
10.1182/blood-2005-06-2216
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发表时间：
2006-06-01
期刊：
影响因子：
20.3
通讯作者：
Keller, Jonathan R.
中科院分区：
文献类型：
--
作者：
Suh, Hyung Chan;Gooya, John;Keller, Jonathan R.
C/EBP α是髓样分化所需的重要转录因子。虽然C/EBP α可以作为细胞命运开关促进双能粒细胞-巨噬细胞祖细胞（GMP）中的粒细胞分化，但其在更原始祖细胞中调节细胞命运决定的作用尚不清楚。我们发现C/EBP α（-/-）胎肝（FL）中红系祖细胞和红系细胞数量增加。此外，造血干细胞中C/EBP α的强制表达通过抑制红系发育和诱导髓系分化导致红系祖细胞的损失和髓系细胞的增加。C/EBPa在小鼠红白血病（MEL）细胞中的条件性表达诱导骨髓特异性基因，同时抑制包括促红细胞生成素受体（EpoR）在内的红细胞特异性基因表达，这表明决定造血细胞命运的新机制。因此，C/EBP α通过抑制多能祖细胞中的红系和诱导髓系基因表达的双重作用在造血细胞命运决定中起作用。
C/EBP alpha is an essential transcription factor required for myeloid differentiation. While C/EBP alpha can act as a cell fate switch to promote granulocyte differentiation in bipotential granulocyte-macrophage progenitors (GMPs), its role in regulating cell fate decisions in more primitive progenitors is not known. We found increased numbers of erythroid progenitors and erythroid cells in C/EBP alpha(-/-) fetal liver (FL). Also, enforced expression of C/EBP alpha in hematopoietic stem cells resulted in a loss of erythroid progenitors and an increase in myeloid cells by inhibition of erythroid development and inducing myeloid differentiation. Conditional expression of C/EBPa in murine erythroleukemia (MEL) cells induced myeloid-specific genes, while inhibiting erythroid-specific gene expression including erythropoietin receptor (EpoR), which suggests a novel mechanism to determine hematopoietic cell fate. Thus, C/EBP alpha functions in hematopoietic cell fate decisions by the dual actions of inhibiting erythroid and inducing myeloid gene expression in multipotential progenitors.