Stepwise reprogramming of B cells into macrophages
Stepwise reprogramming of B cells into macrophages
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DOI：
10.1016/s0092-8674(04)00419-2
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发表时间：
2004-05-28
期刊：
影响因子：
64.5
通讯作者：
Graf, T
中科院分区：
文献类型：
--
作者：
Xie, HF;Ye, M;Graf, T
从多能祖细胞开始，造血谱系由谱系限制转录因子指定。决定淋巴和骨髓细胞命运的转录因子及其潜在机制仍然很大程度上未知。在这里，我们报告了 C/EBPalpha 的强制表达。分化 B 细胞中的 C/EBPbeta 导致其快速有效地重编程为巨噬细胞。 C/EBP 通过抑制 B 细胞定型转录因子 Pax5 诱导这些变化，导致其靶标 CD19 下调，并与 ETS 家族因子内源性 PU.1 协同作用，导致其靶标 Mac-1 和其他骨髓标志物上调。这两个过程可以分离，因为在 PU.1 缺陷的前 B 细胞中，C/EBP 诱导 CD19 下调，但不诱导 Mac-1 激活。我们的观察表明，C/EBPalpha 和 beta 通过一系列需要内源性 PU.1 的并行和顺序变化，将 B 细胞的转录网络重塑为巨噬细胞的转录网络。
Starting with multipotent progenitors, hematopoietic lineages are specified by lineage-restricted transcription factors. The transcription factors that determine the decision between lymphoid and myeloid cell fates, and the underlying mechanisms, remain largely unknown. Here, we report that enforced expression of C/EBPalpha. and C/EBPbeta in differentiated B cells leads to their rapid and efficient reprogramming into macrophages. C/EBPs induce these changes by inhibiting the B cell commitment transcription factor Pax5, leading to the downregulation of its target CD19, and synergizing with endogenous PU.1, an ETS family factor, leading to the upregulation of its target Mac-1 and other myeloid markers. The two processes can be uncoupled, since, in PU.1-deficient pre-B cells, C/EBPs induce CD19 downregulation but not Mac-1 activation. Our observations indicate that C/EBPalpha and beta remodel the transcription network of B cells into that of macrophages through a series of parallel and sequential changes that require endogenous PU.1.