原位测序识别转移早期器官特异性代谢适应
2020-04-01 本文已影响0人
拾光_2020
简介:
本文题为:Flura-seq identifies organ-specific metabolic adaptations during early metastatic colonization,氟尿嘧啶标记的RNA测序识别肿瘤转移早期器官特异性代谢适应。发表于2019年3月26日。
摘要:
转移起始细胞动态适应不同器官的不同微环境,然而由于原位转录组的较低敏感性,转移早期适应现象仍未充分理解。我们创造了高敏感度的氟尿嘧啶标记的RNA测序(Flura-seq)用于原位分析。Flura-seq利用胞嘧啶脱氨酶(cytosine deaminase, CD)将氟胞嘧啶转化为氟尿嘧啶,在稀有细胞群原位对新生RNA进行代谢标记,随后用于纯化和测序。Flura-seq在小鼠异种移植乳腺癌微转移中发现了数百个独特的、动态的、依赖于微环境的器官特异性基因标志物。特别的,与乳腺肿瘤或脑微转移瘤相比,线粒体电子传递复合物I、氧化应激和抗氧化程序在肺部微转移中被诱导。我们在临床样本中证实了肺转移特异性氧化应激的增加和抗氧化程序的上调,从而肯定了在临床应用Flura-seq可以识别转移早期微环境适应性变化。Flura-seq的敏感性、稳健性和经济性在癌症研究之外有着广泛的应用。
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总结
本文主要亮点为发明了一种高度敏感的原位测序技术,该技术可分选并测序微转移细胞内新合成的转录本,最大限度地减小了环境改变的影响,如细胞悬液制备等环节。
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