Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage
Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage
复制标题
DOI：
10.1042/0264-6021:3610621
复制
发表时间：
2002-02-01
影响因子：
4.1
通讯作者：
Binétruy, B
中科院分区：
文献类型：
--
作者：
Bost, F;Caron, L;Binétruy, B
小鼠胚胎干细胞（ES细胞）是可分化为多种细胞谱系的多能细胞。ES细胞向脂肪细胞谱系的定型依赖于用全捕集剂维甲酸（RA）的早期3天处理。为了表征这一过程的分子机制，我们研究了细胞外信号调节激酶（ERK）通路的贡献。用RA处理ES细胞衍生的拟胚体导致ERK通路的延长激活，但不包括c-Jun N-末端激酶、p38丝裂原活化蛋白激酶或磷酸肌醇3-激酶通路。为了研究ERK激活的作用，RA与ERK信号通路的特异性抑制剂PD 98059共同治疗，阻止脂肪细胞形成和脂肪形成标志物、脂肪细胞脂质结合蛋白和过氧化物酶体增殖物激活受体γ的表达。此外，我们发现ERK激活是必需的。仅在RA治疗期间。PD 98059不会干扰ES细胞定向分化为其他谱系，例如神经发生、肌肉发生和心肌发生。与ERK通路在终末分化中有争议的作用相反，我们的研究结果清楚地表明，该通路在脂肪形成的早期阶段是特别需要的，对应于ES细胞的RA依赖性承诺。
Mouse embryonic stem (ES) cells are pluripotent cells that differentiate into multiple cell lineages. The commitment of ES cells into the adipocyte lineage is dependent on an early 3-day treatment with all-traps retinoic acid (RA). To characterize the molecular mechanisms underlying this process, we examined the contribution of the extracellular-signal-regulated kinase (ERK) pathway. Treatment of ES cell-derived embryoid bodies with RA resulted in a prolonged activation of the ERK pathway, but not the c-Jun N-terminal kinase, p38 mitogen-activated protein kinase or phosphoinositide 3-kinase pathways. To investigate the role of ERK activation, co-treatment of RA with PD98059, a specific inhibitor of the ERK signalling pathway, prevented both adipocyte formation and expression of the adipogenic markers, adipocyte lipid-binding protein and peroxisome-proliferator-activated receptor gamma. Furthermore, we show that ERK activation is required. only during RA treatment. PD98059 does not interfere with the commitment of ES cells into other lineages, such as neurogenesis, myogenesis and cardiomyogenesis. As opposed to the controversial role of the ERK pathway in terminal differentiation, our results clearly demonstrate that this pathway is specifically required at an early stage of adipogenesis, corresponding to the RA-dependent commitment of ES cells.