Neural cells play an inhibitory role in pancreatic differentiation of pluripotent stem cells.
Neural cells play an inhibitory role in pancreatic differentiation of pluripotent stem cells.
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DOI：
10.1111/gtc.12308
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Kume S
中科院分区：
文献类型：
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作者：
Nakashima R;Morooka M;Shiraki N;Sakano D;Ogaki S;Kume K;Kume S
来源于胚胎干（ES）细胞和诱导多能干（iPS）细胞的胰腺内分泌β细胞作为治疗药物的筛选系统和基于细胞的治疗的基础而受到关注。在这里，我们使用了小鼠ES细胞的12天β细胞分化方案，并获得了几种促进β细胞分化的命中化合物。这些化合物之一，麦考酚酸（MPA），有效地促进ES细胞分化，伴随着神经元细胞的减少。使用共培养系统表明存在神经细胞源性抑制β细胞分化的体液因子。基于基因阵列分析，我们专注于Wnt/β-catenin通路，并显示Wnt通路抑制剂逆转MPA诱导的β细胞分化。Wnt途径活化也促进人iPS细胞中的β细胞分化。我们的结果表明，Wnt信号传导激活正调控β细胞分化，并代表神经抑制因子的下游靶点。
Pancreatic endocrine β‐cells derived from embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have received attention as screening systems for therapeutic drugs and as the basis for cell‐based therapies. Here, we used a 12‐day β‐cell differentiation protocol for mouse ES cells and obtained several hit compounds that promoted β‐cell differentiation. One of these compounds, mycophenolic acid (MPA), effectively promoted ES cell differentiation with a concomitant reduction of neuronal cells. The existence of neural cell‐derived inhibitory humoral factors for β‐cell differentiation was suggested using a co‐culture system. Based on gene array analysis, we focused on the Wnt/β‐catenin pathway and showed that the Wnt pathway inhibitor reversed MPA‐induced β‐cell differentiation. Wnt pathway activation promoted β‐cell differentiation also in human iPS cells. Our results showed that Wnt signaling activation positively regulates β‐cell differentiation, and represent a downstream target of the neural inhibitory factor.