Common proteomic profiles of induced pluripotent stem cell-derived three-dimensional neurons and brain tissue from Alzheimer patients.
Common proteomic profiles of induced pluripotent stem cell-derived three-dimensional neurons and brain tissue from Alzheimer patients.
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DOI：
10.1016/j.jprot.2018.04.032
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发表时间：
2018-06-30
影响因子：
3.3
通讯作者：
Xia W
中科院分区：
文献类型：
--
作者：
Chen M;Lee HK;Moo L;Hanlon E;Stein T;Xia W
我们建立了一个独特的平台，用于从阿尔茨海默病（AD）患者培养的三维（3D）神经元和脑组织进行蛋白质组学分析。我们收集外周血单个核细胞（PBMC），将PBMC转化为诱导多能干细胞（iPSC）系，并将iPSC分化为人类三维神经球体。将AD患者死后的额上皮层、额下皮层和小脑区域的脑组织与对照组的相同区域进行比较。来自AD受试者的三维神经球体的蛋白质组学分析揭示了一些参与轴突生长、线粒体功能和抗氧化防御的蛋白质的改变。对死后阿尔茨海默病脑组织的类似分析显示，与氧化应激、神经炎症有关的蛋白质以及与轴突损伤有关的蛋白质发生了显著变化。这些结果清楚地表明，在我们的体外环境中，AD患者的3D神经元功能障碍与死后AD脑组织在体内的功能障碍相当。总之，我们的研究揭示了一些在阿尔茨海默病发病机制中具有重要意义的候选蛋白，并支持了ipsc衍生的3D神经元系统作为研究阿尔茨海默病病理新方面的模型的观点。在这项研究中，我们提出了一个独特的平台，用于诱导多能干细胞衍生的三维（3D）神经元的蛋白质组学分析，并将结果与阿尔茨海默病患者和正常对照者死后脑组织的三个区域的结果进行比较。我们的研究结果表明，在我们的体外环境中，AD患者的3D神经元功能障碍与死后AD脑组织在体内相当。我们的研究结果揭示了几个候选蛋白在AD发病机制中具有重要意义。
We established a unique platform for proteomic analysis of cultured three-dimensional (3D) neurons and brain tissue from Alzheimer’s disease (AD) patients. We collected peripheral blood mononuclear cells (PBMC), converted PBMC to induced pluripotent stem cell (iPSC) lines, and differentiated the iPSC into human 3D neuro-spheroids. The postmortem brain tissue from the superior frontal cortex, inferior frontal cortex and cerebellum area of the AD patients was compared to the same regions from the control subjects. Proteomic analysis of 3D neuro-spheroids derived from AD subjects revealed the alteration of a number of proteins involved in axon growth, mitochondrial function, and antioxidant defense. Similar analysis of post-mortem AD brain tissue revealed significant alteration in proteins involved in oxidative stress, neuro-inflammation, along with proteins related to axonal injury. These results clearly indicate that the dysfunction of 3D neurons from AD patients in our in vitro environment is comparable to the post-mortem AD brain tissue in vivo. In conclusion, our study revealed a number of candidate proteins that have important implications in AD pathogenesis and supports the notion that the iPSC-derived 3D neuronal system functions as a model to examine novel aspects of AD pathology. In this study, we present a unique platform for proteomic analysis of induced pluripotent stem cell-derived three dimensional (3D) neurons and compare the results to those from three regions of post-mortem brain tissue from Alzheimer’s disease patients and normal control subjects. Our results show that the dysfunction of 3D neurons from AD patients in our in vitro environment is comparable to the post-mortem AD brain tissue in vivo. Our results revealed several candidate proteins that have important implications in AD pathogenesis.
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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.
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Goldstein, Lawrence S. B.
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作者：
Duan L;Bhattacharyya BJ;Belmadani A;Pan L;Miller RJ;Kessler JA
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影响因子：
6.1
作者：
Dickson, TC;Chuckowree, JA;Vickers, JC
通讯作者：
Vickers, JC
影响因子：
4
作者：
Cuadrado-Tejedor, Mar;Vilarino, Marcos;Perez-Mediavilla, Alberto
通讯作者：
Perez-Mediavilla, Alberto
David Gene功能分类工具：一种以生物模块为中心的新型算法，可在功能上分析大基因列表。
影响因子：
12.3
作者：
Huang, Da Wei;Sherman, Brad T;Tan, Qina;Collins, Jack R;Alvord, W Gregory;Roayaei, Jean;Stephens, Robert;Baseler, Michael W;Lane, H Clifford;Lempicki, Richard A
通讯作者：
Lempicki, Richard A