Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients.
Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients.
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DOI：
10.1038/tp.2014.12
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发表时间：
2014-03-25
影响因子：
6.8
通讯作者：
O'Shea KS
中科院分区：
文献类型：
--
作者：
Chen HM;DeLong CJ;Bame M;Rajapakse I;Herron TJ;McInnis MG;O'Shea KS
双相情感障碍(BP)是一种慢性精神疾病，其特征是情绪从躁狂到抑郁的动态、病理性波动。到目前为止，研究人类神经精神疾病(如BP)的一个主要挑战是有限地获得可存活的中枢神经系统组织来检查疾病进展。患者来源的诱导多能干细胞(IPSCs)现在提供了一个机会来分析神经组织的充分互补和识别新的疾病机制的前景。我们检测了来自特征良好的患者的IPSC分化为神经元时基因表达的变化；IPSC的转录组几乎没有差异，但BP神经元的转录谱明显不同于对照组。与对照组相比，BP神经元膜结合受体和离子通道转录本的表达显著增加，我们发现锂离子对BP神经元胞内钙瞬变和波幅有明显的影响。参与端脑神经元识别的转录因子的表达也发生了变化。对照神经元表达决定背侧端脑命运的转录本，而BP神经元表达与腹侧(内侧神经节隆起)区域分化有关的基因。细胞对背侧/腹侧模式提示有反应，如在两组中加入Hedgehog(腹侧)通路激活剂紫杉胺或背侧剂(锂)刺激NKX2-1(腹侧标识)或EMX2(背侧)表达。以细胞为基础的模型应该对我们理解BP的发生和治疗产生重大影响；IPSC细胞系本身提供了与其他神经发育障碍进行比较的重要资源。
Bipolar disorder (BP) is a chronic psychiatric condition characterized by dynamic, pathological mood fluctuations from mania to depression. To date, a major challenge in studying human neuropsychiatric conditions such as BP has been limited access to viable central nervous system tissue to examine disease progression. Patient-derived induced pluripotent stem cells (iPSCs) now offer an opportunity to analyze the full compliment of neural tissues and the prospect of identifying novel disease mechanisms. We have examined changes in gene expression as iPSC derived from well-characterized patients differentiate into neurons; there was little difference in the transcriptome of iPSC, but BP neurons were significantly different than controls in their transcriptional profile. Expression of transcripts for membrane bound receptors and ion channels was significantly increased in BP-derived neurons compared with controls, and we found that lithium pretreatment of BP neurons significantly altered their calcium transient and wave amplitude. The expression of transcription factors involved in the specification of telencephalic neuronal identity was also altered. Control neurons expressed transcripts that confer dorsal telencephalic fate, whereas BP neurons expressed genes involved in the differentiation of ventral (medial ganglionic eminence) regions. Cells were responsive to dorsal/ventral patterning cues, as addition of the Hedgehog (ventral) pathway activator purmorphamine or a dorsalizing agent (lithium) stimulated expression of NKX2-1 (ventral identity) or EMX2 (dorsal) in both groups. Cell-based models should have a significant impact on our understanding of the genesis and therefore treatment of BP; the iPSC cell lines themselves provide an important resource for comparison with other neurodevelopmental disorders.
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DOI：
10.1176/appi.ajp.2010.10091340
发表时间：
2011-03
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Gershon ES;Alliey-Rodriguez N;Liu C
通讯作者：
Liu C
精神分裂症和躁郁症患者前额皮质中的 MicroRNA 表达谱。
影响因子：
4.5
作者：
Kim, Albert H.;Reimers, Mark;Mahera, Brion;Williamson, Vernell;McMichael, Omari I.;McClay, Joseph L.;van den Oord, Edwin J. C. G.;Riley, Brien P.;Kendler, Kenneth S.;Vladimirov, Vladimir I.
通讯作者：
Vladimirov, Vladimir I.
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.
通讯作者：
Goldstein, Lawrence S. B.
影响因子：
5.4
作者：
Chen H;Wang N;Zhao X;Ross CA;O'Shea KS;McInnis MG
通讯作者：
McInnis MG
影响因子：
11
作者：
Brennand, K. J.;Simone, A.;Tran, N.;Gage, F. H.
通讯作者：
Gage, F. H.