Gastroenterology:激活Wnt信号可刺激肠祖细胞分化

2017-04-06 zhangfan MedSci原创

在人类和小鼠神经祖细胞的研究中, Wnt信号通路可促进体外培养的ENS神经激活

肠神经系统(ENS)神经干细胞和祖细胞有胃肠病治疗的潜力,但对于这类细胞调节增殖和分化的信号机制目前尚不清楚。近日,研究者系统评估了经典神经祖细胞Wnt信号通路对新生小鼠和人类肠道细胞增殖分化的影响。

研究人员首先从野生型C57BL / 6小鼠及wnt1-cre2记者小鼠新生小肠肌层分离祖细胞,之后从接受手术治疗肛门闭锁或局灶性肠穿孔的2个月和7个月龄婴儿肠道组织分离ENS细胞并通过Wnt3a 和SB216763激活β-联蛋白依赖经典Wnt信号通路。研究人员通过免疫印迹和定量PCR来评估Wnt刺激和免疫组织化学,增殖和细胞死亡过程,以确定是否有新的神经元生成。

结果显示,小鼠肠神经祖细胞检测到Wnt受体Frizzled 1-10的表达和共受体LRP5、LRP6表达上调,Wnt受体激动剂药物刺激导致细胞内Wnt依赖β-联蛋白和已知Wnt靶基因AXIN2,LEF1和Lgr5表达上调。经典Wnt信号通路可促进来自小鼠和人的祖细胞生长,表现出细胞扩增以及新生神经元激活的特点。

研究表明,在人类和小鼠神经祖细胞的研究中, Wnt信号通路可促进体外培养的ENS神经激活。ENS祖细胞在Wnt激动剂刺激下的神经源性作用为其在自体细胞替代疗法中的应用提供了直接证据。

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    2017-12-09 许安
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    2017-04-07 zhwj