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Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
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逐步重新编程B细胞变成巨细胞
1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine Cancer Research Center, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Cell
|May 28, 2004
概括
转录因子C/EBPalpha和C/EBPbeta可以将B细胞重新编程成巨细胞. 这涉及抑制Pax5和与PU.1合作,改变细胞命运的决定.
科学领域:
- 血液形成和细胞命运的决定.
- 细胞分化的分子机制
- 免疫中的转录因子网络.
背景情况:
- 造血系起源于多强的祖先,由血系受限的转录因子指导.
- 控制淋巴细胞与骨髓细胞命运决定的特定转录因子尚未完全理解.
- 了解这些因素对于控制免疫细胞发育和功能至关重要.
研究的目的:
- 识别能够将分化B细胞重新编程成其他造血系的转录因子.
- 阐明细胞命运决定被逆转或改变的分子机制.
- 研究B细胞中C/EBPalpha,C/EBPbeta和PU.1对巨细胞重编程的作用.
主要方法:
- 在分化的B细胞中强制表达C/EBPalpha和C/EBPbeta.
- 对关键血统特定基因表达的分析,包括Pax5,CD19,PU.1和Mac-1.
- 使用PU.1-缺乏的B前细胞来剖析个体转录因子的作用的实验.
主要成果:
- 强制C/EBPalpha和C/EBPbeta表达迅速将B细胞重新编程成巨细胞.
- C/EBPs抑制了B细胞因子Pax5,降低了其目标CD19.
- 与内源性PU.1协同作用的C/EBPs可以调节像Mac-1这样的髓质标记物.
- 重编程需要内源性PU.1来激活髓状细胞标记物,尽管CD19下调独立发生.
结论:
- C/EBPalpha和C/EBPbeta是B细胞对巨细胞重编程的强有力的驱动因素.
- 重编程过程涉及通过抑制B细胞因子和激活髓状因子来重塑转录因子网络.
- 内源PU.1对于B细胞的全髓状重编程至关重要,突出显示了转录因子家族之间的关键合作.
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