Butler Alexandra E, Matveyenko Aleksey V, Kirakossian David, Park Johanna, Gurlo Tatyana, Butler Peter C
Larry L. Hillblom Islet Research Center, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
Larry L. Hillblom Islet Research Center, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA ; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
J Histotechnol. 2016;39(2):59-65. doi: 10.1080/01478885.2015.1106073. Epub 2016 May 10.
Laser capture microdissection (LCM) is a powerful method to isolate specific populations of cells for subsequent analysis such as gene expression profiling, for example, microarrays or ribonucleic (RNA)-Seq. This technique has been applied to frozen as well as formalin-fixed, paraffin-embedded (FFPE) specimens with variable outcomes regarding quality and quantity of extracted RNA. The goal of the study was to develop the methods to isolate high-quality RNA from islets of Langerhans and pancreatic duct glands (PDG) isolated by LCM. We report an optimized protocol for frozen sections to minimize RNA degradation and maximize recovery of expected transcripts from the samples using quantitative real-time polymerase chain reaction (RT-PCR) by adding RNase inhibitors at multiple steps during the experiment. This technique reproducibly delivered intact RNA (RIN values 6-7). Using quantitative RT-PCR, the expected profiles of insulin, glucagon, mucin6 (Muc6), and cytokeratin-19 (CK-19) mRNA in PDGs and pancreatic islets were detected. The described experimental protocol for frozen pancreas tissue might also be useful for other tissues with moderate to high levels of intrinsic ribonuclease (RNase) activity.
激光捕获显微切割(LCM)是一种强大的方法,可用于分离特定细胞群体,以便进行后续分析,如基因表达谱分析,例如微阵列或核糖核酸(RNA)测序。该技术已应用于冷冻以及福尔马林固定、石蜡包埋(FFPE)的标本,在提取RNA的质量和数量方面取得了不同的结果。本研究的目的是开发从通过LCM分离的胰岛和胰腺导管腺(PDG)中分离高质量RNA的方法。我们报告了一种针对冷冻切片的优化方案,通过在实验过程中的多个步骤添加核糖核酸酶抑制剂,使用定量实时聚合酶链反应(RT-PCR)来最小化RNA降解并最大化样品中预期转录本的回收率。该技术可重复产生完整的RNA(RIN值为6-7)。使用定量RT-PCR,检测到了PDG和胰岛中胰岛素、胰高血糖素、粘蛋白6(Muc6)和细胞角蛋白19(CK-19)mRNA的预期谱。所描述的冷冻胰腺组织实验方案可能对其他具有中度至高度内源性核糖核酸酶(RNase)活性的组织也有用。