Characterization and transplantation of enteric neural crest cells from human induced pluripotent stem cells.
Characterization and transplantation of enteric neural crest cells from human induced pluripotent stem cells.
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人诱导多能干细胞肠神经嵴细胞的表征和移植。
DOI：
10.1038/mp.2016.191
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发表时间：
2018-03
影响因子：
11
通讯作者：
Xiang AP
中科院分区：
文献类型：
--
作者：
Li W;Huang L;Zeng J;Lin W;Li K;Sun J;Huang W;Chen J;Wang G;Ke Q;Duan J;Lai X;Chen R;Liu M;Liu Y;Wang T;Yang X;Chen Y;Xia H;Xiang AP
肠神经系统（ENS）被认为是第二个大脑，因为它的复杂性和肠功能的自主控制。ENS和中枢神经系统（CNS）之间相互作用的研究进展表明肠/脑轴的改变可能是自闭症谱系障碍（ASD）、帕金森病（PD）和其他人类CNS疾病的病理生理学机制，但由于缺乏良好的模型系统，其潜在机制在很大程度上尚不清楚。人类诱导多能干细胞（hiPSC）具有无限增殖和分化成所有三个胚层细胞的能力，因此使iPSC成为疾病建模和细胞治疗的理想细胞来源。在此，hiPSC被诱导有效地分化为神经嵴干细胞（NCSC）。当与神经节肠组织的平滑肌层共培养时，NCSC分化为表达一氧化氮合酶（nNOS）、血管活性肠多肽（VIP）、胆碱乙酰转移酶（ChAT）或钙维生素A的成熟肠样神经元的不同亚型，具有典型的功能神经元的电生理特征。此外，当它们在卵内、体外或体内移植到无神经节或无神经节的鸡、小鼠或人肠道组织中时，hiPSC衍生的NCSC显示出广泛的迁移和神经分化能力，产生表达肠神经系统特征性表型标志物的神经元和神经胶质细胞。我们的研究结果表明，来源于hiPSC的肠NCSC为研究胃肠道疾病和脑/肠功能障碍的发病机制提供了有力的工具，并代表了肠神经移植治疗的潜在理想细胞来源。
The enteric nervous system (ENS) is recognized as a second brain because of its complexity and its largely autonomic control of bowel function. Recent progress in studying the interactions between the ENS and the central nervous system (CNS) has implicated alterations of the gut/brain axis as a possible mechanism in the pathophysiology of autism spectrum disorders (ASDs), Parkinson’s disease (PD) and other human CNS disorders, whereas the underlying mechanisms are largely unknown because of the lack of good model systems. Human induced pluripotent stem cells (hiPSCs) have the ability to proliferate indefinitely and differentiate into cells of all three germ layers, thus making iPSCs an ideal source of cells for disease modelling and cell therapy. Here, hiPSCs were induced to differentiate into neural crest stem cells (NCSCs) efficiently. When co-cultured with smooth muscle layers of ganglionic gut tissue, the NCSCs differentiated into different subtypes of mature enteric-like neurons expressing nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), choline acetyltransferase (ChAT) or calretinin with typical electrophysiological characteristics of functional neurons. Furthermore, when they were transplanted into aneural or aganglionic chick, mouse or human gut tissues in ovo, in vitro or in vivo, hiPSC-derived NCSCs showed extensive migration and neural differentiation capacity, generating neurons and glial cells that expressed phenotypic markers characteristic of the enteric nervous system. Our results indicate that enteric NCSCs derived from hiPSCs supply a powerful tool for studying the pathogenesis of gastrointestinal disorders and brain/gut dysfunction and represent a potentially ideal cell source for enteric neural transplantation treatments.
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影响因子：
64.8
作者：
Israel, Mason A.;Yuan, Shauna H.;Bardy, Cedric;Reyna, Sol M.;Mu, Yangling;Herrera, Cheryl;Hefferan, Michael P.;Van Gorp, Sebastiaan;Nazor, Kristopher L.;Boscolo, Francesca S.;Carson, Christian T.;Laurent, Louise C.;Marsala, Martin;Gage, Fred H.;Remes, Anne M.;Koo, Edward H.;Goldstein, Lawrence S. B.
通讯作者：
Goldstein, Lawrence S. B.
Connexin 43 参与人类诱导多能干细胞的生成
影响因子：
3.5
作者：
Ke, Qiong;Li, Li;Xiang, Andy Peng
通讯作者：
Xiang, Andy Peng
DOI：
10.1002/aur.1467
发表时间：
2015-10
期刊：
Autism research : official journal of the International Society for Autism Research
影响因子：
--
作者：
Grubišić V;Kennedy AJ;Sweatt JD;Parpura V
通讯作者：
Parpura V
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
23.9
作者：
Kim, Yong Jun;Lim, Hotae;Lee, Gabsang
通讯作者：
Lee, Gabsang