Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders: studies of lysosomal storage diseases and channelopathy.
Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders: studies of lysosomal storage diseases and channelopathy.
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神经元细胞的临床实用性直接从患者的成纤维细胞转化为神经精神疾病：溶酶体储存疾病和通道疗法的研究。
DOI：
10.2174/1566524015666150303110300
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发表时间：
2015
影响因子：
2.5
通讯作者：
Kai M
中科院分区：
文献类型：
--
作者：
Kano S;Yuan M;Cardarelli RA;Maegawa G;Higurashi N;Gaval-Cruz M;Wilson AM;Tristan C;Kondo MA;Chen Y;Koga M;Obie C;Ishizuka K;Seshadri S;Srivastava R;Kato TA;Horiuchi Y;Sedlak TW;Lee Y;Rapoport JL;Hirose S;Okano H;Valle D;O'Donnell P;Sawa A;Kai M
从人类成纤维细胞（诱导神经元（iN）细胞）中直接产生功能性神经细胞的方法最近得到了发展，但迄今为止的研究只集中在技术上的改进或已知病理表型的再现上。一个关键的问题是，这种新技术是否有助于阐明新的疾病机制或评估治疗策略。在这里，我们通过研究Tay-Sachs病（一种代表性的溶酶体贮积病）和Dravet综合征（一种婴儿期严重肌阵挛性癫痫）来解决这个问题，使用具有未成熟有丝分裂后谷氨酸能神经元细胞特征的人类in细胞。在Tay-Sachs病中，我们已经成功地描述了典型的神经元病理，GM2神经节苷脂的大量积累，并证明了这种新型细胞培养对未来药物筛选的适用性。在Dravet综合征中，我们发现了一种新的功能表型，这是经典小鼠模型和人类尸检大脑研究中没有发现的。综上所述，本研究表明，人类iN细胞可用于转化神经科学研究，以探索新的疾病机制和评估治疗性化合物。在未来，利用具有良好基因组图谱特征的人类In细胞的研究可以整合到神经精神疾病的多学科患者导向研究中，以解决新的疾病机制和评估治疗策略。
Methodologies for generating functional neuronal cells directly from human fibroblasts [induced neuronal (iN) cells] have been recently developed, but the research so far has only focused on technical refinements or recapitulation of known pathological phenotypes. A critical question is whether this novel technology will contribute to elucidation of novel disease mechanisms or evaluation of therapeutic strategies. Here we have addressed this question by studying Tay-Sachs disease, a representative lysosomal storage disease, and Dravet syndrome, a form of severe myoclonic epilepsy in infancy, using human iN cells with feature of immature postmitotic glutamatergic neuronal cells. In Tay-Sachs disease, we have successfully characterized canonical neuronal pathology, massive accumulation of GM2 ganglioside, and demonstrated the suitability of this novel cell culture for future drug screening. In Dravet syndrome, we have identified a novel functional phenotype that was not suggested by studies of classical mouse models and human autopsied brains. Taken together, the present study demonstrates that human iN cells are useful for translational neuroscience research to explore novel disease mechanisms and evaluate therapeutic compounds. In the future, research using human iN cells with well-characterized genomic landscape can be integrated into multidisciplinary patient-oriented research on neuropsychiatric disorders to address novel disease mechanisms and evaluate therapeutic strategies.
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影响因子：
3.6
作者：
Higurashi N;Uchida T;Lossin C;Misumi Y;Okada Y;Akamatsu W;Imaizumi Y;Zhang B;Nabeshima K;Mori MX;Katsurabayashi S;Shirasaka Y;Okano H;Hirose S
通讯作者：
Hirose S
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.
通过确定的因素将成纤维细胞直接转化为功能性神经元。
影响因子：
64.8
作者：
Vierbuchen, Thomas;Ostermeier, Austin;Pang, Zhiping P.;Kokubu, Yuko;Suedhof, Thomas C.;Wernig, Marius
通讯作者：
Wernig, Marius
影响因子：
64.5
作者：
Dolmetsch R;Geschwind DH
通讯作者：
Geschwind DH
影响因子：
120.7
作者：
Meikle, PJ;Hopwood, JJ;Carey, WF
通讯作者：
Carey, WF