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Author:
Date:
2016-07-20
[Abstract] Neuroblast migration is a major component in the process of neuronal circuit assembly. In the rodent postnatal brain, the subependymal zone (SEZ) is the largest neurogenic niche where new neurons are born throughout life. These cells migrate several millimeters following a specific pathway called the rostral migratory stream (RMS) towards the olfactory bulb. Once they reach their final destination, they differentiate mainly as interneurons and integrate into already established neuronal circuits. Along the RMS, neuroblasts use a particular mode of migration known as chain migration. They stay attached to each other while migrating and are intimately associated with adjacent astrocytic processes. To dissect the molecular and cellular signals involved in neuroblast migration, we developed ...
[摘要] 神经母细胞迁移是神经元电路组装过程中的主要组成部分。 在啮齿动物出生后的大脑中，子宫颈区（SEZ）是新生神经元生命中最大的神经源性生态位。 这些细胞沿着称为传播流（RMS）的特定途径朝向嗅球迁移几毫米。 一旦达到其最终目的地，它们主要区分为中间神经元并整合到已建立的神经元回路中。 沿着RMS，神经母细胞使用称为链转移的特定迁移模式。 它们在迁移时保持相互依赖，并与相邻的星形细胞过程密切相关。 为了解剖神经母细胞迁移中涉及的分子和细胞信号，我们开发了一种体外系统，其由在星形胶质细胞单层顶部共培养的经SEZ衍生的外植体组成。
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Author:
Date:
2014-04-05
[Abstract] Tumour microenvironment and cancer-associated fibroblasts in particular exhibit tumour promoting abilities that are not present in their normal counterparts (Calvo et al., 2013; Hanahan and Coussens, 2012). Therefore, functional and molecular characterization of the modifications occurring in fibroblasts during tumour progression is essential to fully understand their role in tumour progression. Previous studies have addressed this issue using human fibroblasts and comparing normal and adjacent fibroblasts to tumour-associated fibroblasts (Kalluri and Zeisberg, 2006). However, these studies are hampered by the intrinsic variability of human samples (e.g. pairing, age, genomic landscape, etc). In order to overcome these issues, we used a fully characterised ...
[摘要] 肿瘤微环境和癌相关成纤维细胞特别表现出其正常对应物中不存在的肿瘤促进能力（Calvo等人，2013; Hanahan和Coussens，2012）。因此，在肿瘤进展期间发生在成纤维细胞中的修饰的功能和分子表征是完全理解它们在肿瘤进展中的作用所必需的。以前的研究已经解决了这个问题使用人类成纤维细胞和比较正常和相邻成纤维细胞与肿瘤相关的成纤维细胞（Kalluri和Zeisberg，2006）。然而，这些研究受到人类样品的内在变异性（例如配对，年龄，基因组景观，等）的阻碍。为了克服这些问题，我们使用了完全表征的小鼠乳腺癌模型MMTV-PyMT（Guy等人，1992; Lin等人，2003）。 MMTV-PyMT转基因小鼠在小鼠乳腺肿瘤病毒启动子/增强子的指导下表达多瘤病毒中T抗原。这是一个多焦点管腔乳腺癌模型，经历良好定义和特征阶段（即增生，腺瘤，癌和浸润性癌）。有趣的是，这种模型有100％的发病率，是非常结构性的（呈现高浓度的成纤维细胞），并引起肺自发转移80-94％的发病率。重要的是，至少对于腹股沟乳腺（腺4和9），不同的肿瘤阶段与小鼠的年龄很好相关：在6周龄时出现的增生，6-8周龄之间的腺瘤，癌和侵袭性癌症从8周开始。该模型使我们可靠地分离来自不同肿瘤阶段的成纤维细胞，并仔细表征其功能和分子性质（Calvo等人，2013）。
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