In vitro enhanced differentiation of neural networks in ES gut-like organ from mouse ES cells by a 5-HT4-receptor activation
In vitro enhanced differentiation of neural networks in ES gut-like organ from mouse ES cells by a 5-HT4-receptor activation
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DOI：
10.1016/j.bbrc.2011.02.072
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发表时间：
2011-03-25
影响因子：
3.1
通讯作者：
Kuniyasu, Hiroki
中科院分区：
文献类型：
--
作者：
Takaki, Miyako;Misawa, Hiromi;Kuniyasu, Hiroki
利用胚胎体（EB）培养系统，我们从小鼠胚胎干细胞（ES gut）中培养出功能器官样簇，即“肠道”。每个ES肠表现出不同类型的自发运动。在这些自发收缩的ES肠道中，Cajal （ICC) （c-kit，一种具有酪氨酸激酶活性的跨膜受体）间质细胞、阳性细胞、肠道起搏器细胞）和平滑肌细胞密集分布，但未发现肠道神经网络。在本研究中，我们仅在EB形成过程中添加5- ht4受体（SR4）激动剂柠檬酸莫沙必利（1-10 μ M），成功地形成了致密的肠内神经网络。添加sr4拮抗剂GR113808 （10 μ M）可消除sr4拮抗剂诱导的肠道神经网络的形成。SR4激动剂（1 μ M）上调SR4 mRNA的表达，而SR4拮抗剂则消除这种上调。5-HT本身具有与sr4激动剂相似的效果，但效力较弱。这些结果表明5r4激动剂分化了肠内神经网络，通过激活ES肠内的SR4介导。(C) 2011爱思唯尔公司版权所有。
Using an embryoid body (EB) culture system, we developed a functional organ-like cluster, a "gut", from mouse embryonic stem (ES) cells (ES gut). Each ES gut exhibited various types of spontaneous movements. In these spontaneously contracting ES guts, dense distributions of interstitial cells of Cajal (ICC) (c-kit, a transmembrane receptor that has tyrosine kinase activity, positive cells; gut pacemaker cells) and smooth muscle cells were discernibly identified, but enteric neural networks were not identified. In the present study, we succeeded in forming dense enteric neural networks by a 5-HT4-receptor (SR4) agonist, mosapride citrate (1-10 mu M) added only during EB formation. Addition of an SR4-antagonist, GR113808 (10 mu M) abolished the SR4-agonist-induced formation of enteric neural networks. The SR4-agonist (1 mu M) up-regulated the expression of mRNA of SR4 and the SR4-antagonist abolished this upregulation. 5-HT per se exerted similar effects to those of SR4-agonist, though less potent. These results suggest 5R4-agonist differentiated enteric neural networks, mediated via activation of SR4 in the ES gut. (C) 2011 Elsevier Inc. All rights reserved.