Wacker Michael J, Tehel Michelle M, Gallagher Philip M
Department of Basic Medical Science, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA.
J Appl Physiol (1985). 2008 Jul;105(1):308-15. doi: 10.1152/japplphysiol.00897.2007. Epub 2008 May 8.
The use of single-cell quantitative RT-PCR has greatly aided the study of gene expression in fields such as muscle physiology. For this study, we hypothesized that single muscle fibers from a biopsy can be placed directly into the reverse transcription buffer and that gene expression data can be obtained without having to first extract the RNA. To test this hypothesis, biopsies were taken from the vastus lateralis of five male subjects. Single muscle fibers were isolated and underwent RNA isolation (technique 1) or placed directly into reverse transcription buffer (technique 2). After cDNA conversion, individual fiber cDNA was pooled and quantitative PCR was performed using primer-probes for beta(2)-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, insulin-like growth factor I receptor, and glucose transporter subtype 4. The no RNA extraction method provided similar quantitative PCR data as that of the RNA extraction method. A third technique was also tested in which we used one-quarter of an individual fiber's cDNA for PCR (not pooled) and the average coefficient of variation between fibers was <8% (cycle threshold value) for all genes studied. The no RNA extraction technique was tested on isolated muscle fibers using a gene known to increase after exercise (pyruvate dehydrogenase kinase 4). We observed a 13.9-fold change in expression after resistance exercise, which is consistent with what has been previously observed. These results demonstrate a successful method for gene expression analysis directly from single muscle fibers.
单细胞定量逆转录聚合酶链反应的应用极大地促进了肌肉生理学等领域的基因表达研究。在本研究中,我们假设取自活检的单根肌纤维可直接放入逆转录缓冲液中,且无需先提取RNA就能获得基因表达数据。为验证这一假设,从五名男性受试者的股外侧肌获取活检样本。分离出单根肌纤维,分别进行RNA提取(技术1)或直接放入逆转录缓冲液中(技术2)。在进行cDNA转换后,将单个纤维的cDNA混合,使用针对β2 -微球蛋白、甘油醛-3-磷酸脱氢酶、胰岛素样生长因子I受体和葡萄糖转运蛋白4亚型的引物探针进行定量PCR。不进行RNA提取的方法所提供的定量PCR数据与RNA提取方法相似。还测试了第三种技术,即我们使用单个纤维cDNA的四分之一进行PCR(不混合),对于所有研究的基因,纤维间的平均变异系数<8%(循环阈值)。使用已知运动后会增加的基因(丙酮酸脱氢酶激酶4)在分离的肌纤维上测试了不进行RNA提取的技术。我们观察到抗阻运动后表达有13.9倍的变化,这与之前观察到的结果一致。这些结果证明了一种直接从单根肌纤维进行基因表达分析的成功方法。