上海典奥生物科技有限公司 
首页 | 今日动态 | 生物通商城 | 人才市场 | 核心刊物 | 特价专栏 | BBS交流 | 新技术专栏 | 会展中心 | 技术期刊 | 技术讲座 | 龙虎榜
 
地址:上海浦东新区东靖路1831号3楼301室,201208 
联系人:刘映薇
电话:021-5860.5185-822
传真:021-5890.1159
邮箱:marketing@tekon.com.cn
网址:www.tekontech.com

 

 
你的位置 》首页 》公司信息 》阅读信息
IncuCyte实时动态活细胞成像仪在神经科学领域的文献综述

IncuCyte实时动态活细胞成像仪在神经科学领域的文献综述

上海典奥生物科技有限公司(Tekon Biotech (Shanghai) Ltd.

 

总述:

IncuCyte实时动态活细胞成像仪已被广泛用于长时间实时监控神经元的培养,定量与神经科学研究相关的细胞行为。下面着重介绍了应用IncuCyte实时动态活细胞成像仪的最新文献报道,展示了实时的、非侵入的、基于图像的测量方法的价值,并揭示了Incucyte神经发生(neurogenesis神经退变(neurodegeneration机理的洞察力,提供了与“神经生长条件”(neurogenic conditions)相关的基因表型特征的研究方法,以及在神经干细胞研究neuronal stem cell research)中的贡献。

 

已有研究使用IncuCyte对神经突生长、细胞迁移和增殖的检测来确定神经毒性(neurotoxic)和神经保护性(neuroprotective)处理的影响(Tortoriello et al., 2014; Woo et al., 2014),探测控制CNS修复的通路(Oudin et al., 2011)并描述神经元干细胞的生长情况(Gòmez-Lòpez et al., 2011)。当IncuCyte和其他终点成像仪器或生化检测方法联合使用时,IncuCyte的实时细胞动态数据可用来解释神经元培养中发生的不可预料的时序事件(Lodge et al. 2010)并解决基于时间的神经保护处理效果(Lu et al. 2013)。

 

查找IncuCyte的所有公开发表文献列表,请访问我们的在线文献库:

 http://www.essenbioscience.com/resources/publications/

产品介绍:

http://www.ebiotrade.com/instrument/instrument_productDetail.aspx?productID=34b740d2-750c-41f8-b837-eeb2e2228d6e

 

神经毒性和神经形成

研究者使用IncuCyte对神经突生长和神经元运动进行检测,预测了神经毒性和神经保护性处理的影响(Tortoriello et al., 2014; Woo et al., 2014),探索控制神经发生的机制(Oudin et al., 2011)。

 

Tortoriello, G. et al. Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J. 1–18 (2014).

 

在一个合作的研究中,瑞典斯德哥尔摩卡洛琳斯卡医学院的研究者检测了大麻的主要神经活性成分THCΔ9-tetrahydrocannabinol)对原代皮层神经元的神经毒性影响。结果表明在胚胎期接触大麻的儿童引发神经行为损害和认知损害危险的可能性更大,但是与THC是否有关还无法确定。

 

IncuCyte的高清晰度相差成像和整合的神经跟踪成像分析模组(NeuroTrack image analysis module)被用来动态地定量非标记实验中的THC对神经突生长的影响。细胞处理前的读取确保了对照组和实验组在THC处理之前在表型上的一致性。与空白对照组对比,THC处理会损害皮层神经元的神经突形成,该结果支持了作者的结论: THC处理会引起SCG10的降解,它是轴突延伸过程中一种调控生长锥形成的蛋白质,是第一个已知的中枢神经系统发展中THC的分子靶点。

 

Oudin, M. J. et al. Endocannabinoids regulate the migration of subventricular zone-derived neuroblasts in the postnatal brain. J. Neurosci. 31, 4000–11 (2011).

 

Oudin等人(英国伦敦国王学院)使用IncuCyte实时动态活细胞成像仪研究了内源性大麻素(endocannabinoideCB)信号在成人神经发生中的作用。成人脑内的神经干细胞(NS cells)通过增殖和分化产生新的神经元,迁移到嗅球中生长。重要的是,越来越多的证据表明,eCB信号可调控神经干细胞从嗅球中转移到大脑受损部位的能力,修复受损的功能。IncuCyte细胞迁移实验可用来描述eCB受体,CB1CB2,在原代神经干细胞迁移中的功能。选择性小分子拮抗剂的药理抑制作用引起了神经干细胞迁移的大规模减少,同时还抑制了甘油二酯脂酶的活性,后者是脑内合成eCB主要的酶。与此相反,使用CB1CB3激动剂活化大麻素受体极大地促进了划痕愈合的速度,而与选择性CB1CB3拮抗剂联合使用时,结果恰恰相反。这些结果支持eCB系统在神经干细胞迁移中的新作用,也表明了它在调控成人神经发生中的重要性。

 

进一步的阅读如下:

Tortoriello, G. et al. Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J. 1–18 (2014).

Wiszniak, S. et al. The ubiquitin ligase Nedd4 regulates craniofacial development by promoting cranial neural crest cell survival and stem-cell like properties. Dev. Biol. 383, 186–200 (2013).

Oudin, M. J. et al. Endocannabinoids regulate the migration of subventricular zone-derived neuroblasts in the postnatal brain. J. Neurosci. 31, 4000–11 (2011).

Wicki-Stordeur, L. E. & Swayne, L. A. Panx1 regulates neural stem and progenitor cell behaviours associated with cytoskeletal dynamics and interacts with multiple cytoskeletal elements. Cell Commun. Signal. 11, 62 (2013).

Williams, G. et al. Transcriptional basis for the inhibition of neural stem cell proliferation and migration by the TGFβ-family member GDF11. PLoS One 8, e78478 (2013).

Parmentier-Batteur, S. et al. Attenuation of scratch-induced reactive astrogliosis by novel EphA4 kinase inhibitors. J. Neurochem. 118, 1016–31 (2011).

 

 

神经退变

IncuCyte实时动态活细胞成像仪可以对神经退变表型进行细致的观察(McLean et al. 2014), 非标记模型的开发,概述了蛋白聚集介导的神经元的死亡过程和药物处理的时序性变化(Lu et al. 2013)。这些模型操作简单,可实现高通量流程化,同时还可以使用Essen BioScience CellPlayer Caspase-3/7凋亡荧光检测试剂对神经毒性进行测量(Yao et al. 2013)。

 

Lu, B. et al. Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance. Nat. Neurosci. 16, 562–70 (2013).

Lu, B. & Palacino, J. A novel human embryonic stem cell-derived Huntington’s disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT-dependent neurodegeneration. FASEB J. 27, 1820–9 (2013).

 

中国上海复旦大学的研究者和诺华合作,使用IncuCyte技术对一种新的亨廷顿舞蹈症(Huntington’s disease)模型进行了表型描述。亨廷顿舞蹈症(HD)由变异的亨廷顿(mhtt)蛋白中的聚谷氨酰胺(polyQ)重复的扩增引发。PolyQ的长度如果超过36个重复,就可引起功能毒性,而且重复的数目与亨廷顿舞蹈症的严重程度成正比。鲁教授等人开发了一种新型的hESC来源的神经亨廷顿舞蹈症模型,既展示了不溶性的变异亨廷顿(mHTT)蛋白的聚集,也展示了可溶性的亨廷顿蛋白引起的神经退变。IncuCyte的高清晰度相差图像和融合率算法被用来对细胞形态进行细致的评估,并对神经退变的表型进行实时定量。IncuCyte的实时数据显示,用siRNA敲除mHTT后细胞恢复的表型与siRNA浓度是相关的,并且可以计算达到指定神经退变程度所需的时间——这对于跨研究对比是极有价值的参考。作者开发了一种高通量的,可得到丰富数据的IncuCyte筛选实验流程,进行易于实行的亨廷顿舞蹈症的毒性遗传修饰因子的筛选,这种方法可以准确地测量神经细胞死亡的动态过程(Yao et al. 2013)。

 

在第二篇论文中,鲁教授等人开发了来源于亨廷顿舞蹈症患者诱导多能干细胞(iPSCs)的神经元细胞。使用Essen BioScience CellPlayer Caspase-3/7凋亡试剂,他们展示了在缺少BDNFcaspase的活性降低到了野生型细胞中HTT siRNA敲除后的水平。这些结果揭示了在缺少BDNF的条件下的基于mHTT的神经毒性。IncuCyte还可用于确认NUB1(泛素类蛋白1的负调控因子)在疾病神经元中过度表达时,该神经元受保护而不会进行caspase-3介导的凋亡。这些数据得到的结论是:NUB1mHTT诱导的毒性的抑制剂,可成为新型的治疗亨廷顿的候选。

 

进一步的阅读如下:

Lu, B. et al. Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance. Nat. Neurosci. 16, 562–70 (2013).

Lu, B. & Palacino, J. A novel human embryonic stem cell-derived Huntington’s disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT-dependent neurodegeneration. FASEB J. 27, 1820–9 (2013).

Lazzeroni, G. et al. A phenotypic screening assay for modulators of huntingtin-induced transcriptional dysregulation. J. Biomol. Screen. 18, 984–96 (2013).

Yao, Y. et al. High-throughput high-content detection of genetic modifiers of neurodegeneration in human stem cell derived neurons. Protoc. Exch. (2013).

McLean, J. R. et al. ALS-associated peripherin spliced transcripts form distinct protein inclusions that are neuroprotective against oxidative stress. Exp. Neurol. (2014).

 

神经发生的条件:

基因过表达和缺失的特征

无需荧光标记就能对神经突的动态变化进行实时测量,这点被用于检测基因异常的表型结果和神经发生的关系,如唐氏综合症(Down)和2q23.1微缺失综合症(Soppa et al. 2014; Camarena et al. 2014)。

 

Soppa, U. et al. The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation. Cell Cycle 13, 2084–100 (2014).

 

德国亚琛大学的研究者使用IncuCyte的融合率和荧光测量参数,并结合IncuCyte NeuroTrack分析软件探索了DYRK1A(唐氏综合症的候选基因)在人神经元模型中的过表达的影响。IncuCyte高清晰度的相差图像揭示了DYRK1A的过表达引起了增殖的停滞,但不会引起细胞死亡——用平行阻抗的研究方法无法得出这个结论,但被IncuCyte GFP细胞核计数方法进一步证实。与此相反,激酶活性缺乏点突变基因(DYRK1A-KR)的过表达对增殖没有影响,显示生长抑制依赖于DYRK1A激酶的活性。用IncuCyte NeuroTrack分析软件对神经突产物的自动分析证实:与DYRK1A-KR过度表达细胞相比,DYRK1A的长期过表达大幅度地增加了单位细胞的总神经突长度。这个结论阐述了一个新的机制, DYRK1A的过表达可能促进未成熟的神经元分化,并改变了唐氏综合症患者的大脑发育。

Camarena, V. et al. Disruption of Mbd5 in mice causes neuronal functional deficits and neurobehavioral abnormalities consistent with 2q23.1 microdeletion syndrome. EMBO Mol. Med. 1–13 (2014).

 

2q23.1微缺失综合症由MBD5基因的缺失引起,症状特点为无学习能力、行为困难和颅面骨畸形。美国迈阿密大学和日本熊本大学合作,运用IncuCyte NeuroTrack模组探索一个新型的携带MBD5插入突变的小鼠模型。从杂合的突变鼠中分离出的皮层神经元培养显示神经突生长和分支受到了损伤。作者得出结论:此发现暗示了MBD5在神经调控中的作用,并支持MBD52q23.1微缺失综合症有因果关系。

 

神经干细胞:

特征,分化和在筛选中的应用

IncuCyte实时动态活细胞成像仪被用来研究神经干细胞增殖的特征(Sun et al. 2011),探索控制自我更新的遗传因子(Gòmez-Lòpez et al., 2011)和识别引起神经元分化的因素(Lodge et al. 2010)。整合的IncuCyte NeuroTrack软件可以用来实时的定量神经元分化(Efthymiou et al. 2014)和基于图像的筛选,使用神经干细胞,寻找脑肿瘤治疗的新方法(Danovi et al. 2013)。

 

Lodge, A. P. et al. Performance of mouse neural stem cells as a screening reagent: characterization of PAC1 activity in medium-throughput functional assays. J. Biomol. Screen. 15, 159–68 (2010).

 

GSK的研究者描述了鼠神经干细胞(mNSC)被用于生理功能相关试剂筛选时的形态特征和长期生长/分化特征。研究人员使用IncuCyte的融合率计算方法检测了不同生长因子条件对增殖的影响和天然表达的神经肽受体PAC1(脑垂体腺苷酸环化酶激活肽受体1)对增殖的功能。令人惊讶的是高浓度PAC1配体PACAP-38的刺激极大地降低了培养70h后的mNSC的融合率。此观察有助于解决两种同一终点时间检测细胞增殖的方法间的矛盾。在存在不同浓度的PACAP-38时,固定染色后荧光显微镜记录了mNSC细胞数目的急剧减少,而用ATP检测法估计的细胞数目仍保持在高位。研究IncuCyte随时间进行的成像结果显示,PACAP-38诱导的融合率的减少是由细胞表型的显著变化和神经分化引起的。综合以上研究,作者得出结论:高浓度的PACAP-38诱导了mNSC的分化,同时引起了未发生凋亡的细胞的代谢活性增加。

 

Efthymiou, A. et al. Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells. J. Biomol. Screen. 19, 32–43 (2014).

 

美国贝塞斯达国立卫生研究院(NIH)的Efthymiou和其同事描述了一种方法,能将来源于人多能干细胞(PSCs)的神经元纯种群进行培养,以生成大量的来源于病人的神经元细胞,从而进行神经退行性疾病的高通量表型筛选。IncuCyteNeuroTrack图像分析模组被用来监控神经突的长度,此神经突长度可作为人多能干细胞来源的神经元成熟的标志。作者指出,对神经元表型变化的实时监测是成功研究疾病的关键,因为该疾病影响了突触的发育和轴突的生长。这些数据还为高通量筛选来源于神经退行性疾病病人的神经元铺平了道路。

Danovi, D. et al. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One 8, e77053 (2013).

 

伦敦大学学院(UCL)筛选了针对正常干细胞(NS)和胶质母细胞瘤来源的神经干细胞(GNS)的化合物库,以寻找治疗多形性胶质母细胞瘤(Glioblastoma MultiformeGM)的新疗法。GM是最常见的和最恶性的原发性脑肿瘤,目前还没有治疗方法。IncuCyte被用来确定能选择性的对GNS细胞产生细胞毒性和细胞抑制而不会干扰NS细胞增殖的小分子。160种激酶抑制剂在96孔板上针对3种病人来源的GNS细胞系进行了测试。用IncuCyte采集细胞增殖高清晰度的相差图像,然后使用软件(Cell-Profiler)进行处理和分析定量。基于形态参数,对每个时间点的有丝分裂细胞的数目进行了定量。此次筛选确认了化合物JNJ-10198409J101)可在GNS细胞而不是NS细胞中引起有丝分裂阻滞。随后的蛋白质组学分析表明J101可能抑制了类似马球的激酶1PLK-1),它是一种G2/M转换早期的感受器。进一步研究使用已知有效和特异的Plk1抑制剂模拟了J101处理后的表型,选择性针对GNS细胞。Plk1抑制剂开发可能为开发新型的胶质母细胞瘤治疗药带来新的希望。

进一步的阅读如下:

Lodge, A. P., Langmead, C. J., Daniel, G., Anderson, G. W. & Werry, T. D. Performance of mouse neural stem cells as a screening reagent: characterization of PAC1 activity in medium-throughput functional assays. J. Biomol. Screen. 15, 159–68 (2010).

Gómez-López, S. et al. Sox2 and Pax6 maintain the proliferative and developmental potential of gliogenic neural stem cells In vitro. Glia 59, 1588–99 (2011).

Efthymiou, A. et al. Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells. J. Biomol. Screen. 19, 32–43 (2014).

Sun, Y., Hu, J., Zhou, L., Pollard, S. M. & Smith, A. Interplay between FGF2 and BMP controls the self-renewal, dormancy and differentiation of rat neural stem cells. J. Cell Sci. 124, 1867–77 (2011).

Danovi, D. et al. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One 8, e77053 (2013).

Tailor, J. et al. Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency. J. Neurosci. 33, 12407–22 (2013).

 

作者:Tim O‘CallaghanEssen BioScience的应用支持科学家。他回顾了IncuCyte在神经科学研究应用的文献,揭示了研究者是如何运用IncuCyte实时成像来得到神经科学领域新发现的。通过广泛研究资料里的各种主题,Tim总结了研究者是如何运用IncuCyte来进行神经毒性的实时监测,探索指导神经发生的信号通路和神经发生条件中的候选基因的作用。

 

 

Neuroscience Publications List – By Topic

Neurotoxicity and neurogenesis

1. Tortoriello, G. et al. Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J. 1–18 (2014). doi:10.1002/embj.201386035

 

2. Wiszniak, S. et al. The ubiquitin ligase Nedd4 regulates craniofacial development by promoting cranial neural crest cell survival and stem-cell like properties. Dev. Biol. 383, 186–200 (2013).

 

3. Wicki-Stordeur, L. E. & Swayne, L. A. Panx1 regulates neural stem and progenitor cell behaviours associated with cytoskeletal dynamics and interacts with multiple cytoskeletal elements. Cell Commun. Signal. 11, 62 (2013).

 

4. Nam, S. T. et al. Insect peptide CopA3-induced protein degradation of p27Kip1 stimulates proliferation and protects neuronal cells from apoptosis. Biochem. Biophys. Res. Commun. 437, 35–40 (2013).

 

5. Oudin, M. J. et al. Endocannabinoids regulate the migration of subventricular zone-derived neuroblasts in the postnatal brain. J. Neurosci. 31, 4000–11 (2011).

 

6. Parmentier-Batteur, S. et al. Attenuation of scratch-induced reactive astrogliosis by novel EphA4 kinase inhibitors. J. Neurochem. 118, 1016–31 (2011).

 

7. Goncalves, M. B. et al. The COX-2 inhibitors, meloxicam and nimesulide, suppress neurogenesis in the adult mouse brain. Br. J. Pharmacol. 159, 1118–25 (2010).

 

8. Niego, B. et al. Thrombin-induced activation of astrocytes in mixed rat hippocampal cultures is inhibited by soluble thrombomodulin. Brain Res. 1381, 38–51 (2011).

 

9. Wan Woo, K. et al. Phenolic derivatives from the rhizomes of Dioscorea nipponica and their anti-neuroinflammatory and neuroprotective activities. J. Ethnopharmacol. 1–7 (2014). doi:10.1016/j.jep.2014.06.043

 

10. Sidrauski, C. et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2, e00498 (2013).

Neuro-degeneration

1. McLean, J. R. et al. ALS-associated peripherin spliced transcripts form distinct protein inclusions that are neuroprotective against oxidative stress. Exp. Neurol. (2014). doi:10.1016/j.expneurol.2014.05.024

 

2. Lu, B. & Palacino, J. A novel human embryonic stem cell-derived Huntington’s disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT-dependent neurodegeneration. FASEB J. 27, 1820–9 (2013).

 

3. Lu, B. et al. Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance. Nat. Neurosci. 16, 562–70 (2013).

 

4. Lazzeroni, G. et al. A phenotypic screening assay for modulators of huntingtin-induced transcriptional dysregulation. J. Biomol. Screen. 18, 984–96 (2013).

 

5. Yao, Y. et al. High-throughput high-content detection of genetic modifiers of neurodegeneration in human stem cell derived neurons. Protoc. Exch. (2013). doi:10.1038/protex.2013.085

Neuro-genetic conditions

1. Soppa, U. et al. The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation. Cell Cycle 13, 2084–100 (2014).

 

2. Camarena, V. et al. Disruption of Mbd5 in mice causes neuronal functional deficits and neurobehavioral abnormalities consistent with 2q23.1 microdeletion syndrome. EMBO Mol. Med. 1–13 (2014). doi:10.15252/emmm.201404044

Neuronal stem cells

1. Efthymiou, A. et al. Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells. J. Biomol. Screen. 19, 32–43 (2014).

 

2. Ninomiya, E. et al. Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells. Springerplus 3, 527 (2014).

 

3. Danovi, D. et al. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One 8, e77053 (2013).

 

4. Tailor, J. et al. Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency. J. Neurosci. 33, 12407–22 (2013).

 

5. Williams, G. et al. Transcriptional basis for the inhibition of neural stem cell proliferation and migration by the TGFβ-family member GDF11. PLoS One 8, e78478 (2013).

 

6. Mclaren, D. et al. Automated large-scale culture and medium-throughput chemical screen for modulators of proliferation and viability of human induced pluripotent stem cell-derived neuroepithelial-like stem cells. J. Biomol. Screen. 18, 258–68 (2013).

 

7. Falk, A. et al. Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons. PLoS One 7, e29597 (2012).

 

8. Sun, Y. et al. Interplay between FGF2 and BMP controls the self-renewal, dormancy and differentiation of rat neural stem cells. J. Cell Sci. 124, 1867–77 (2011).

 

9. Gómez-López, S. et al. Sox2 and Pax6 maintain the proliferative and developmental potential of gliogenic neural stem cells In vitro. Glia 59, 1588–99 (2011).

 

10. Lodge, A. P. et al.. Performance of mouse neural stem cells as a screening reagent: characterization of PAC1 activity in medium-throughput functional assays. J. Biomol. Screen. 15, 159–68 (2010).

 

11. Sun, Y. et al. Long-term tripotent differentiation capacity of human neural stem (NS) cells in adherent culture. Mol. Cell. Neurosci. 38, 245–58 (2008).

Neuro-oncology

1. Mulcahy Levy, J. M. et al. Autophagy Inhibition Improves Chemosensitivity in BRAFV600E Brain Tumors. Cancer Discov. (2014). doi:10.1158/2159-8290.CD-14-0049

 

2. Balvers, R. K. et al. Serum-free culture success of glial tumors is related to specific molecular profiles and expression of extracellular matrix-associated gene modules. Neuro. Oncol. 15, 1684–95 (2013).

 

3. Presneau, N. et al. MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a tumour suppressor gene involved in tumour progression. Br. J. Cancer 108, 964–72 (2013).

 

4. Liu, Z. et al. CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression. Cell Death Differ. 18, 1174–83 (2011).

 

5. Ward, R. J. et al. Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma. Cancer Res. 69, 4682–90 (2009).

 

6. Pollard, S. M. et al. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 4, 568–80 (2009).

 

7. Camand, E., Peglion, F., Osmani, N., Sanson, M. & Etienne-Manneville, S. N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration. J. Cell Sci. 125, 844–57 (2012).

 

8. Danovi, D. et al. High content screening of defined chemical libraries using normal and glioma-derived neural stem cell lines. Methods Enzymol. 506, 311–29 (2012).

 

9. Danovi, D. et al. Imaging-based chemical screens using normal and glioma-derived neural stem cells. Biochem. Soc. Trans. 38, 1067–71 (2010).

 

10. Galavotti, S. et al. The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells. Oncogene 32, 699–712 (2013).

 

Neuroscience Publications List – By First Author

1. Balvers, R. K. et al. Serum-free culture success of glial tumors is related to specific molecular profiles and expression of extracellular matrix-associated gene modules. Neuro. Oncol. 15, 1684–95 (2013).

 

2. Camand, E., Peglion, F., Osmani, N., Sanson, M. & Etienne-Manneville, S. N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration. J. Cell Sci. 125, 844–57 (2012).

3. Camarena, V. et al. Disruption of Mbd5 in mice causes neuronal functional deficits and neurobehavioral abnormalities consistent with 2q23.1 microdeletion syndrome. EMBO Mol. Med. 1–13 (2014). doi:10.15252/emmm.201404044

4. Danovi, D. et al. Imaging-based chemical screens using normal and glioma-derived neural stem cells. Biochem. Soc. Trans. 38, 1067–71 (2010).

5. Danovi, D. et al. High content screening of defined chemical libraries using normal and glioma-derived neural stem cell lines. Methods Enzymol. 506, 311–29 (2012).

6. Danovi, D. et al. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One 8, e77053 (2013).

7. Efthymiou, A. et al. Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells. J. Biomol. Screen. 19, 32–43 (2014).

8. Falk, A. et al. Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons. PLoS One 7, e29597 (2012).

9. Galavotti, S. et al. The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells. Oncogene 32, 699–712 (2013).

10. Gómez-López, S. et al. Sox2 and Pax6 maintain the proliferative and developmental potential of gliogenic neural stem cells In vitro. Glia 59, 1588–99 (2011).

11. Goncalves, M. B. et al. The COX-2 inhibitors, meloxicam and nimesulide, suppress neurogenesis in the adult mouse brain. Br. J. Pharmacol. 159, 1118–25 (2010).

12. Lazzeroni, G. et al. A phenotypic screening assay for modulators of huntingtin-induced transcriptional dysregulation. J. Biomol. Screen. 18, 984–96 (2013).

13. Liu, Z. et al. CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression. Cell Death Differ. 18, 1174–83 (2011).

14. Lodge, A. P. et al. Performance of mouse neural stem cells as a screening reagent: characterization of PAC1 activity in medium-throughput functional assays. J. Biomol. Screen. 15, 159–68 (2010).

15. Lu, B. et al. Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance. Nat. Neurosci. 16, 562–70 (2013).

16. Lu, B. & Palacino, J. A novel human embryonic stem cell-derived Huntington’s disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT-dependent neurodegeneration. FASEB J. 27, 1820–9 (2013).

17. Mclaren, D. et al. Automated large-scale culture and medium-throughput chemical screen for modulators of proliferation and viability of human induced pluripotent stem cell-derived neuroepithelial-like stem cells. J. Biomol. Screen. 18, 258–68 (2013).

18. McLean, J. R. et al. ALS-associated peripherin spliced transcripts form distinct protein inclusions that are neuroprotective against oxidative stress. Exp. Neurol. (2014). doi:10.1016/j.expneurol.2014.05.024

19. Mulcahy Levy, J. M. et al. Autophagy Inhibition Improves Chemosensitivity in BRAFV600E Brain Tumors. Cancer Discov. (2014). doi:10.1158/2159-8290.CD-14-0049

 

20. Nam, S. T. et al. Insect peptide CopA3-induced protein degradation of p27Kip1 stimulates proliferation and protects neuronal cells from apoptosis. Biochem. Biophys. Res. Commun. 437, 35–40 (2013).

21. Niego, B. et al. Thrombin-induced activation of astrocytes in mixed rat hippocampal cultures is inhibited by soluble thrombomodulin. Brain Res. 1381, 38–51 (2011).

22. Ninomiya, E. et al. Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells. Springerplus 3, 527 (2014).

23. Oudin, M. J. et al. Endocannabinoids regulate the migration of subventricular zone-derived neuroblasts in the postnatal brain. J. Neurosci. 31, 4000–11 (2011).

24. Parmentier-Batteur, S. et al. Attenuation of scratch-induced reactive astrogliosis by novel EphA4 kinase inhibitors. J. Neurochem. 118, 1016–31 (2011).

25. Pollard, S. M. et al. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 4, 568–80 (2009).

26. Presneau, N. et al. MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a tumour suppressor gene involved in tumour progression. Br. J. Cancer 108, 964–72 (2013).

27. Sidrauski, C. et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2, e00498 (2013).

28. Soppa, U. et al. The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation. Cell Cycle 13, 2084–100 (2014).

29. Sun, Y. et al. Interplay between FGF2 and BMP controls the self-renewal, dormancy and differentiation of rat neural stem cells. J. Cell Sci. 124, 1867–77 (2011).

30. Sun, Y. et al. Long-term tripotent differentiation capacity of human neural stem (NS) cells in adherent culture. Mol. Cell. Neurosci. 38, 245–58 (2008).

31. Tailor, J. et al. Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency. J. Neurosci. 33, 12407–22 (2013).

32. Tortoriello, G. et al. Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J. 1–18 (2014). doi:10.1002/embj.201386035

33. Wan Woo, K. et al. Phenolic derivatives from the rhizomes of Dioscorea nipponica and their anti-neuroinflammatory and neuroprotective activities. J. Ethnopharmacol. 1–7 (2014). doi:10.1016/j.jep.2014.06.043

34. Ward, R. J. et al. Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma. Cancer Res. 69, 4682–90 (2009).

35. Wicki-Stordeur, L. E. & Swayne, L. A. Panx1 regulates neural stem and progenitor cell behaviours associated with cytoskeletal dynamics and interacts with multiple cytoskeletal elements. Cell Commun. Signal. 11, 62 (2013).

36. Williams, G. et al. Transcriptional basis for the inhibition of neural stem cell proliferation and migration by the TGFβ-family member GDF11. PLoS One 8, e78478 (2013).

37. Wiszniak, S. et al. The ubiquitin ligase Nedd4 regulates craniofacial development by promoting cranial neural crest cell survival and stem-cell like properties. Dev. Biol. 383, 186–200 (2013).

38. Yao, Y. et al. High-throughput high-content detection of genetic modifiers of neurodegeneration in human stem cell derived neurons. Protoc. Exch. (2013). doi:10.1038/protex.2013.085