c-Maf plays a crucial role for the definitive erythropoiesis that accompanies erythroblastic island formation in the fetal liver
c-Maf plays a crucial role for the definitive erythropoiesis that accompanies erythroblastic island formation in the fetal liver
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DOI：
10.1182/blood-2010-08-300400
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发表时间：
2011-08-04
期刊：
影响因子：
20.3
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
--
作者：
Kusakabe, Manabu;Hasegawa, Kazuteru;Takahashi, Satoru
c-Maf是属于碱性亮氨酸拉链蛋白的活化蛋白-1超家族的大Maf（肌肉腱膜纤维肉瘤）转录因子之一。尽管其在血液恶性肿瘤中过度表达，但c-Maf在正常造血中发挥的生理作用在很大程度上尚未探索。在C57 BL/6 J背景下，c-Maf（-/-）胚胎在胚胎第（E）15天和E18天之间死于严重的红斑狼疮。胎肝细胞的流式细胞术分析显示，与c-Maf（-/-）同窝仔相比，c-Maf（-/-）胚胎中的成熟红细胞区室显著减少。有趣的是，CFU测定表明c-Maf（-/-）和c-Maf（-/-）胎肝细胞在红系集落计数方面没有显著差异。该结果表明，c-Maf（-/-）胚胎中受损的定形红细胞生成是由于非细胞自主效应，表明胎儿肝脏中有缺陷的红细胞生成微环境。正如预期的那样，在c-Maf（-/-）胚胎中，成红细胞岛中巨噬细胞周围的成红细胞数量显著减少。此外，在c-Maf（-/-）胎肝巨噬细胞中观察到VCAM-1表达降低。总之，这些结果强烈表明，c-Maf是决定性的红细胞生成在胎肝中至关重要的，在巨噬细胞，构成成红细胞岛中发挥重要作用。（血。2011; 118（5）：1374-1385）
c-Maf is one of the large Maf (musculoaponeurotic fibrosarcoma) transcription factors that belong to the activated protein-1 super family of basic leucine zipper proteins. Despite its overexpression in hematologic malignancies, the physiologic roles c-Maf plays in normal hematopoiesis have been largely unexplored. On a C57BL/6J background, c-Maf(-/-) embryos succumbed from severe erythropenia between embryonic day (E) 15 and E18. Flow cytometric analysis of fetal liver cells showed that the mature erythroid compartments were significantly reduced in c-Maf(-/-) embryos compared with c-Maf(-/-) littermates. Interestingly, the CFU assay indicated there was no significant difference between c-Maf(-/-) and c-Maf(-/-) fetal liver cells in erythroid colony counts. This result indicated that impaired definitive erythropoiesis in c-Maf(-/-) embryos is because of a non-cell-autonomous effect, suggesting a defective erythropoietic microenvironment in the fetal liver. As expected, the number of erythroblasts surrounding the macrophages in erythroblastic islands was significantly reduced in c-Maf(-/-) embryos. Moreover, decreased expression of VCAM-1 was observed in c-Maf(-/-) fetal liver macrophages. In conclusion, these results strongly suggest that c-Maf is crucial for definitive erythropoiesis in fetal liver, playing an important role in macrophages that constitute erythroblastic islands. (Blood. 2011; 118(5): 1374-1385)