Direct Reprogramming of Mouse Embryonic Fibroblasts to Conventional Type 1 Dendritic Cells by Enforced Expression of Transcription Factors
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Author:
Date:
2020-05-20
[Abstract] Ectopic expression of transcription factor combinations has been recently demonstrated to reprogram differentiated somatic cells towards the dendritic cell (DC) lineage without reversion to a multipotent state. DCs have the ability to induce potent and long-lasting adaptive immune responses. In particular, conventional type 1 DCs (cDC1s) excel on antigen cross-presentation, a critical step for inducing CD8+ T cell cytotoxic responses. The rarity of naturally occurring cDC1s and lack of in vitro methodologies for the generation of pure cDC1 populations strongly hinders the ...
[摘要] [摘要] 转录因子组合的异位表达最近被证明可以将分化的体细胞重编程为树突状细胞(DC)谱系,而不会回复到多能状态。DC具有诱导有效和持久的适应性免疫应答的能力。在特定的常规类型1的DC(cDC1s)练成抗原交叉呈递,用于诱导CD8的关键步骤+ T细胞的细胞毒性应答。天然存在的cDC1的稀有性和缺乏用于生成纯cDC1群体的体外方法论,严重阻碍了对cDC1谱系规格和功能的研究。在这里,我们描述了用于生成感应DC(iDC)的协议 慢病毒介导的转录因子PU.1,IRF8和BATF3在小鼠胚胎成纤维细胞中的表达。iDC 在9天内获得DC形态,cDC1表型和转录特征。使用此协议生成的iDC 具有对炎症刺激,吞噬死细胞,将抗原加工并交叉呈递给CD8 + T细胞的功能。DC重新编程提供了一个简单易处理的系统,可以生成大量的cDC1类细胞用于高内涵筛选,从而开辟了新途径,可以更好地了解cDC1的规格和功能。将来,在成纤维细胞中忠实诱导cDC1命运可能会导致产生患者特定的疫苗接种DC。
[背景技术树突状细胞(DC)是专业的抗原呈递细胞,专门用于识别,加工和呈递T细胞抗原,在诱导适应性免疫应答和免疫记忆中起关键作用(Me rad 等,2013)。DC可以分为4个主要子集:浆细胞样DC(pDC ),大量1型干扰素的产生者,循环单核细胞衍生的单核细胞衍生DC 和常规DC(cDC ...
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Isolation of Primary Breast Cancer Cells from HER2 Transgenic Mice
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Author:
Date:
2016-10-05
[Abstract] HER2 is a tyrosine kinase receptor, which is overexpressed in about 30% of breast cancer patients. Its overexpression leads to mammary tumorigenesis and increased invasion and metastasis (Slamon et al., 1987). HER2 transgenic mouse (FVB/N-MMTVneu mouse) is a well-established model of mammary tumor in human (Fantozzi and Christofori, 2006). Although in vivo models are excellent for assessing the influence of various factors, especially microenvironment, on development of breast cancer, a convenient and less costly way to study the underlying molecular events is utilizing ...
[摘要] HER2是酪氨酸激酶受体,其在约30%的乳腺癌患者中过表达。 其过表达导致乳腺肿瘤发生和增加的侵袭和转移(Slamon等人,1987)。 HER2转基因小鼠(FVB/N-MMTVneu小鼠)是人类乳腺肿瘤的良好建立的模型(Fantozzi和Christofori,2006)。 虽然体内模型对于评估各种因素,特别是微环境对乳腺癌发展的影响是极好的,但是一种方便且成本较低的研究基础分子事件的方法是利用来自模型的细胞 评价。 为了探索HOXB7抑制起始,但促进乳腺肿瘤转移的分子机制,我们从HER2转基因小鼠产生小鼠乳腺癌细胞系(Liu等人,2015)。 该方案可用于从具有其他遗传背景的小鼠产生乳腺癌细胞系。
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Colon Cancer-associated Fibroblast Establishment and Culture Growth
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Author:
Date:
2016-04-05
[Abstract] Cancer-associated fibroblasts (CAFs) are one of the major players in tumor-stroma crosstalk. Findings in experimental studies suggest important roles for CAFs in regulation of tumor growth, metastasis and drug response (Hanahan and Coussens, 2012). Furthermore, their clinical relevance is supported by new findings from tumor analyses, demonstrating the prognostic and response-predictive significance of CAF-derived markers or gene signatures (Berdiel-hacer et al., 2014; Finak et al., 2008; Navab et al., 2011; Paulsson and Micke, 2014). CAFs are a heterogeneous pool ...
[摘要] 癌症相关成纤维细胞(CAF)是肿瘤 - 基质串扰的主要参与者之一。实验研究的结果表明CAFs在肿瘤生长,转移和药物反应的调节中的重要作用(Hanahan和Coussens,2012)。此外,它们的临床相关性得到来自肿瘤分析的新发现的支持,表明CAF衍生的标记或基因特征的预后和应答预测显着性(Berdiel-hacer等人,2014; Finak 等人,2008; Navab等人,2011; Paulsson和Micke,2014)。 CAF是具有不同功能的细胞亚群的异质池,其需要由它们的标记表达更好地定义。开发用于建立源自人结肠肿瘤的成纤维细胞原代培养物的方法允许我们表征其功能和分子性质(Herrera等人,2013)。此外,CAF影响肿瘤生长和转移的不同分子机制仍有待澄清。因此,癌症相关成纤维细胞的功能和分子表征是完全了解他们在肿瘤进展中的作用的必要条件。
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