Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy.
Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy.
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DOI：
10.1016/j.isci.2021.103140
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发表时间：
2021-10-22
期刊：
影响因子：
5.8
通讯作者：
Aoi T
中科院分区：
文献类型：
--
作者：
Taniguchi-Ikeda M;Koyanagi-Aoi M;Maruyama T;Takaori T;Hosoya A;Tezuka H;Nagase S;Ishihara T;Kadoshima T;Muguruma K;Ishigaki K;Sakurai H;Mizoguchi A;Novitch BG;Toda T;Watanabe M;Aoi T
福山先天性肌营养不良症（Fukuyama congenital muscular dystrophy， FCMD）是一种严重的、难治的遗传性疾病，可影响骨骼肌、眼睛和大脑，其病因是α -肌营养不良（αDG） o -甘露糖基化缺陷。我们以前建立了口蹄疫疾病模型；然而，他们并没有完全概括在人类患者中观察到的表型。在这项研究中，我们从人口蹄疫患者身上获得了诱导多能干细胞（iPSCs），并将这些细胞分化为三维脑类器官和骨骼肌。脑类器官成功地模拟了现有模型无法可靠再现的患者表型，包括α - dg糖基化降低和放射状胶质（RG）纤维迁移异常。碱性多环化合物甘露聚糖-007 （Mn007）在脑和肌肉模型中恢复α - dg糖基化，部分恢复皮质类器官中观察到的异常RG纤维迁移。因此，我们的研究强调了α - dg o -甘露糖基聚糖对正常RG纤维结构和皮质发生中适当的神经元迁移的重要性。ipsc衍生的脑类器官表现出与手足口病患者相似的结构缺陷。手足口病类器官表现出α-DG糖基化降低和径向胶质细胞迁移异常。神经科学;组织工程
Fukuyama congenital muscular dystrophy (FCMD) is a severe, intractable genetic disease that affects the skeletal muscle, eyes, and brain and is attributed to a defect in alpha dystroglycan (αDG) O-mannosyl glycosylation. We previously established disease models of FCMD; however, they did not fully recapitulate the phenotypes observed in human patients. In this study, we generated induced pluripotent stem cells (iPSCs) from a human FCMD patient and differentiated these cells into three-dimensional brain organoids and skeletal muscle. The brain organoids successfully mimicked patient phenotypes not reliably reproduced by existing models, including decreased αDG glycosylation and abnormal radial glial (RG) fiber migration. The basic polycyclic compound Mannan-007 (Mn007) restored αDG glycosylation in the brain and muscle models tested and partially rescued the abnormal RG fiber migration observed in cortical organoids. Therefore, our study underscores the importance of αDG O-mannosyl glycans for normal RG fiber architecture and proper neuronal migration in corticogenesis. FCMD muscle and brain defects result from reduced α-dystroglycan (α-DG) glycosylation iPSC-derived brain organoids exhibit structural defects like those seen in FCMD patients FCMD organoids exhibit decreased α-DG glycosylation and abnormal radial glial migrations Mannan-007 partially restored α-DG glycosylation and radial glial migration defects Pathophysiology; Neuroscience; Tissue Engineering
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小脑颗粒细胞迁移所需的神经胶质支架取决于多糖果作为基底膜蛋白的受体。
影响因子：
7.1
作者：
Nguyen H;Ostendorf AP;Satz JS;Westra S;Ross-Barta SE;Campbell KP;Moore SA
通讯作者：
Moore SA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Lui JH;Hansen DV;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
23.9
作者：
Kim D;Kim CH;Moon JI;Chung YG;Chang MY;Han BS;Ko S;Yang E;Cha KY;Lanza R;Kim KS
通讯作者：
Kim KS
胶质细胞和神经元肌营养不良聚糖在发育中和成年小鼠大脑中的独特功能。
DOI：
10.1523/jneurosci.3247-10.2010
发表时间：
2010-10-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Satz JS;Ostendorf AP;Hou S;Turner A;Kusano H;Lee JC;Turk R;Nguyen H;Ross-Barta SE;Westra S;Hoshi T;Moore SA;Campbell KP
通讯作者：
Campbell KP