Stehling-Sun Sandra, Dade Jessica, Nutt Stephen L, DeKoter Rodney P, Camargo Fernando D
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Nat Immunol. 2009 Mar;10(3):289-96. doi: 10.1038/ni.1694. Epub 2009 Jan 25.
Despite advances in the identification of lymphoid-restricted progenitor cells, the transcription factors essential for their generation remain to be identified. Here we describe an unexpected function for the myeloid oncogene product Mef2c in lymphoid development. Mef2c deficiency was associated with profound defects in the production of B cells, T cells, natural killer cells and common lymphoid progenitor cells and an enhanced myeloid output. In multipotent progenitors, Mef2c was required for the proper expression of several key lymphoid regulators and restriction of the myeloid fate. Our studies also show that Mef2c was a critical transcriptional target of the transcription factor PU.1 during lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network that regulates cell fate 'choice' in multipotent progenitors.
尽管在鉴定淋巴样限制性祖细胞方面取得了进展，但对于其产生所必需的转录因子仍有待确定。在此，我们描述了髓系癌基因产物Mef2c在淋巴细胞发育中的意外功能。Mef2c缺陷与B细胞、T细胞、自然杀伤细胞和常见淋巴样祖细胞产生的严重缺陷以及髓系输出增强有关。在多能祖细胞中，Mef2c是几个关键淋巴细胞调节因子正确表达和限制髓系命运所必需的。我们的研究还表明，Mef2c是淋巴细胞生成过程中转录因子PU.1的关键转录靶点。因此，Mef2c是调节多能祖细胞中细胞命运“选择”的转录网络的关键组成部分。
