Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia.
Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia.
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DOI：
10.1038/mp.2014.22
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发表时间：
2015-03
影响因子：
11
通讯作者：
Gage, F. H.
中科院分区：
文献类型：
--
作者：
Brennand, K.;Savas, J. N.;Kim, Y.;Tran, N.;Simone, A.;Hashimoto-Torii, K.;Beaumont, K. G.;Kim, H. J.;Topol, A.;Ladran, I.;Abdelrahim, M.;Matikainen-Ankney, B.;Chao, S-H;Mrksich, M.;Rakic, P.;Fang, G.;Zhang, B.;Yates, J. R., III;Gage, F. H.
与最近的报道一致，表明从人诱导的多能干细胞（hiPSC）体外分化的神经元相对于人脑中的神经元是不成熟的，我们的hiPSC衍生的神经元与艾伦BrainSpan图谱的基因表达比较表明它们最类似于胎儿脑组织。这一发现表明，基于hiPSC的模型可能更适合研究疾病易感性，而不是对精神分裂症（SZ）的晚期特征进行建模。我们现在报道，SZ hiPSC衍生的神经元的基因签名的显著部分在SZ hiPSC神经祖细胞（NPC）中是保守的。我们使用了两个独立的发现为基础的方法-微阵列基因表达和稳定同位素标记的氨基酸在细胞培养（SILAC）定量蛋白质组学质谱分析，以确定在SZ hiPSC NPC从四个SZ患者的细胞表型。根据我们的发现，SZ hiPSC NPC显示与细胞骨架重塑和氧化应激相关的异常基因表达和蛋白水平，我们预测并随后观察到SZ hiPSC NPC中的异常迁移和增加的氧化应激。这些可重复的NPC表型是通过可扩展的测定法鉴定的，这些测定法可应用于SZ患者的扩展队列，使其成为研究有助于SZ的发育机制的潜在有价值的工具。
Consistent with recent reports indicating that neurons differentiated in vitro from human-induced pluripotent stem cells (hiPSCs) are immature relative to those in the human brain, gene expression comparisons of our hiPSC-derived neurons to the Allen BrainSpan Atlas indicate that they most resemble fetal brain tissue. This finding suggests that, rather than modeling the late features of schizophrenia (SZ), hiPSC-based models may be better suited for the study of disease predisposition. We now report that a significant fraction of the gene signature of SZ hiPSC-derived neurons is conserved in SZ hiPSC neural progenitor cells (NPCs). We used two independent discovery-based approaches—microarray gene expression and stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomic mass spectrometry analyses—to identify cellular phenotypes in SZ hiPSC NPCs from four SZ patients. From our findings that SZ hiPSC NPCs show abnormal gene expression and protein levels related to cytoskeletal remodeling and oxidative stress, we predicted, and subsequently observed, aberrant migration and increased oxidative stress in SZ hiPSC NPCs. These reproducible NPC phenotypes were identified through scalable assays that can be applied to expanded cohorts of SZ patients, making them a potentially valuable tool with which to study the developmental mechanisms contributing to SZ.
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影响因子：
9.9
作者：
Wang, I-Ming;Zhang, Bin;Roberts, Christopher
通讯作者：
Roberts, Christopher
影响因子：
23.9
作者：
Delaloy C;Liu L;Lee JA;Su H;Shen F;Yang GY;Young WL;Ivey KN;Gao FB
通讯作者：
Gao FB
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
23.9
作者：
Maroof, Asif M.;Keros, Sotirios;Tyson, Jennifer A.;Ying, Shui-Wang;Ganat, Yosif M.;Merkle, Florian T.;Liu, Becky;Goulburn, Adam;Stanley, Edouard G.;Elefanty, Andrew G.;Widmer, Hans Ruedi;Eggan, Kevin;Goldstein, Peter A.;Anderson, Stewart A.;Studer, Lorenz
通讯作者：
Studer, Lorenz
DOI：
10.1073/pnas.0905696106
发表时间：
2009-09-22
影响因子：
11.1
作者：
Meechan, Daniel W.;Tucker, Eric S.;LaMantia, Anthony-Samuel
通讯作者：
LaMantia, Anthony-Samuel