Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease.
Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease.
复制标题
来源于发育中纹状体的诱导多能干细胞作为亨廷顿病细胞替代疗法的潜在供体来源。
DOI：
10.1016/j.jcyt.2020.06.001
复制
发表时间：
2021-03
期刊：
影响因子：
4.5
通讯作者：
Rosser AE
中科院分区：
文献类型：
--
作者：
Choompoo N;Bartley OJM;Precious SV;Vinh NN;Schnell C;Garcia A;Roberton VH;Williams NM;Kemp PJ;Kelly CM;Rosser AE
亨廷顿病 (HD) 的细胞替代疗法 (CRT) 需要能够恢复因 STR 退化而丧失的功能的纹状体 (STR) 祖细胞来源。真实的 STR 祖细胞可以从胎儿假定的纹状体或整个神经节隆起 (WGE) 中收集，但这些组织对于广泛的临床应用仍然不切实际，并且需要替代的供体来源。在这里，我们开始探索源自 WGE 的诱导多能干细胞 (iPSC) 可能保留其起源组织的表观遗传记忆的可能性，这可能会增强它们分化为 STR 细胞的能力。我们从人 WGE (hWGE) 中产生了四个 iPSC 系，并确定它们在分化为 STR 表型的能力方面与人胚胎干细胞相似，通过关键 STR 基因的表达和去甲基化来测量，同时保持总体上不同的甲基化组。最后，我们证明这些 STR 分化的 hWGE iPSC 在体外和移植到 HD 模型后与 hWGE（即真实的 STR 组织）具有相同的特征。总体而言，源自人类 WGE 的 iPSC 显示出作为 HD CRT 供体来源的前景。
Cell replacement therapy (CRT) for Huntington disease (HD) requires a source of striatal (STR) progenitors capable of restoring the function lost due to STR degeneration. Authentic STR progenitors can be collected from the fetal putative striatum, or whole ganglionic eminence (WGE), but these tissues remain impractical for widespread clinical application, and alternative donor sources are required. Here we begin exploring the possibility that induced pluripotent stem cells (iPSC) derived from WGE may retain an epigenetic memory of their tissue of origin, which could enhance their ability to differentiate into STR cells. We generate four iPSC lines from human WGE (hWGE) and establish that they have a capacity similar to human embryonic stem cells with regard to their ability to differentiate toward an STR phenotype, as measured by expression and demethylation of key STR genes, while maintaining an overall different methylome. Finally, we demonstrate that these STR-differentiated hWGE iPSCs share characteristics with hWGE (i.e., authentic STR tissues) both in vitro and following transplantation into an HD model. Overall, iPSCs derived from human WGE show promise as a donor source for CRT for HD.
登录
查看更多内容
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
48
作者：
Yusa, Kosuke;Rad, Roland;Takeda, Junji;Bradley, Allan
通讯作者：
Bradley, Allan
影响因子：
5.2
作者：
Nicoleau, Camille;Varela, Christine;Perrier, Anselme L.
通讯作者：
Perrier, Anselme L.
DOI：
10.1073/pnas.0808488105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Aubry, Laetitia;Bugi, Aurore;Perrier, Anselme L.
通讯作者：
Perrier, Anselme L.
影响因子：
23.9
作者：
Hiler D;Chen X;Hazen J;Kupriyanov S;Carroll PA;Qu C;Xu B;Johnson D;Griffiths L;Frase S;Rodriguez AR;Martin G;Zhang J;Jeon J;Fan Y;Finkelstein D;Eisenman RN;Baldwin K;Dyer MA
通讯作者：
Dyer MA