Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines.
Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines.
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DOI：
10.1186/s13041-016-0267-6
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发表时间：
2016-10-03
期刊：
影响因子：
3.6
通讯作者：
Okano H
中科院分区：
文献类型：
--
作者：
Fujimori K;Tezuka T;Ishiura H;Mitsui J;Doi K;Yoshimura J;Tada H;Matsumoto T;Isoda M;Hashimoto R;Hattori N;Takahashi T;Morishita S;Tsuji S;Akamatsu W;Okano H
患者特异性诱导多能干细胞（iPSC）有助于了解疾病的病因、新药的发现和新型治疗干预措施的开发。用于产生iPSC的细胞的常用起始来源是从皮肤活检分离的真皮成纤维细胞（DF）。然而，也有许多储存库含有从各种患者产生的淋巴母细胞样B细胞系（LCL）。到目前为止，这种丰富的LCL生物资源尚未充分用于产生iPSC，它的使用将大大扩大可以通过使用患者特异性iPSC研究的靶向疾病的范围。然而，目前尚不清楚患者的LCL衍生的iPSC（LiPSC）是否可以作为疾病模型。因此，我们产生了帕金森病患者特异性的LiPSC，并评估了它们作为神经系统疾病建模工具的效用。我们通过使用现有的非整合附加型方案，从两个LCL克隆中建立了iPSC，这两个LCL克隆来自健康供体和携带PARK 2突变的患者。全基因组测序（WGS）和比较基因组杂交（CGH）分析表明，iPSC基因组中体细胞变异的外观根据原始细胞类型（LCL，T细胞和成纤维细胞）没有显著变化。此外，通过使用直接神经球转化方法（dNS方法），LiPSC可以分化为功能性神经元，并且它们显示出与DF-iPSCs相似的几种帕金森病表型。这些数据表明，全球LCL库可以用作生成iPSC和疾病模型的资源。因此，LCL是产生iPSC和模拟神经系统疾病的强大工具。本文的在线版本（doi：10.1186/s13041-016-0267-6）包含补充材料，可供授权用户使用。
Patient-specific induced pluripotent stem cells (iPSCs) facilitate understanding of the etiology of diseases, discovery of new drugs and development of novel therapeutic interventions. A frequently used starting source of cells for generating iPSCs has been dermal fibroblasts (DFs) isolated from skin biopsies. However, there are also numerous repositories containing lymphoblastoid B-cell lines (LCLs) generated from a variety of patients. To date, this rich bioresource of LCLs has been underused for generating iPSCs, and its use would greatly expand the range of targeted diseases that could be studied by using patient-specific iPSCs. However, it remains unclear whether patient’s LCL-derived iPSCs (LiPSCs) can function as a disease model. Therefore, we generated Parkinson’s disease patient-specific LiPSCs and evaluated their utility as tools for modeling neurological diseases. We established iPSCs from two LCL clones, which were derived from a healthy donor and a patient carrying PARK2 mutations, by using existing non-integrating episomal protocols. Whole genome sequencing (WGS) and comparative genomic hybridization (CGH) analyses showed that the appearance of somatic variations in the genomes of the iPSCs did not vary substantially according to the original cell types (LCLs, T-cells and fibroblasts). Furthermore, LiPSCs could be differentiated into functional neurons by using the direct neurosphere conversion method (dNS method), and they showed several Parkinson’s disease phenotypes that were similar to those of DF-iPSCs. These data indicate that the global LCL repositories can be used as a resource for generating iPSCs and disease models. Thus, LCLs are the powerful tools for generating iPSCs and modeling neurological diseases. The online version of this article (doi:10.1186/s13041-016-0267-6) contains supplementary material, which is available to authorized users.
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影响因子：
5.2
作者：
Okada, Yohei;Matsumoto, Arifumi;Okano, Hideyuki
通讯作者：
Okano, Hideyuki
影响因子：
23.9
作者：
Loh YH;Hartung O;Li H;Guo C;Sahalie JM;Manos PD;Urbach A;Heffner GC;Grskovic M;Vigneault F;Lensch MW;Park IH;Agarwal S;Church GM;Collins JJ;Irion S;Daley GQ
通讯作者：
Daley GQ
影响因子：
20.3
作者：
Choi, Su Mi;Liu, Hua;Jang, Yoon-Young
通讯作者：
Jang, Yoon-Young
影响因子：
0.4
作者：
Koh, Kishin;Ishiura, Hiroyuki;Takiyama, Yoshihisa
通讯作者：
Takiyama, Yoshihisa
DOI：
10.1093/bioinformatics/btp352
发表时间：
2009-08-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Li H;Handsaker B;Wysoker A;Fennell T;Ruan J;Homer N;Marth G;Abecasis G;Durbin R;1000 Genome Project Data Processing Subgroup
通讯作者：
1000 Genome Project Data Processing Subgroup