Regulation of Gene Expression Is Linked to Life Span in Adult Drosophila

Examination of gene expression and aging in adult Drosophila reveals that the expression of some genes is regulated by age-dependent mechanisms. Genetic mutations, Hyperkinetic(1) and Shaker(5), which are known to shorten life span through an acceleration of the aging process, were used to study the expression of an enhancer trap marked gene. The temporal pattern of expression for such a marked gene shows scaling with respect to life span; it is altered in direct proportion to the life expectancy of the adult animal. This demonstrates that expression of this gene is controlled through mechanisms coupled to physiologic as opposed to chronologic age. Results provide direct evidence for linkage between the regulation of gene expression and life span and establish a model system for the genetic analysis of aging.     

Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation

Understanding how human cardiomyocytes mature is crucial to realizing stem cell-based heart regeneration, modeling adult heart diseases, and facilitating drug discovery. However, it is not feasible to analyze human samples for maturation due to inaccessibility to samples while cardiomy-ocytes mature during fetal development and childhood, as well as difficulty in avoiding variations among individuals. Using model animals such as mice can be a useful strategy;nonetheless, it is not well-understood whether and to what degree gene expression profiles during maturation are shared between humans and mice. Therefore, we performed a comparative gene expression analysis of mice and human samples. First, we examined two distinct mice microarray platforms for shared gene expression profiles, aiming to increase reliability of the analysis. We identified a set of genes display-ing progressive changes during maturation based on principal component analysis. Second, we demonstrated that the genes identified had a differential expression pattern between adult and ear-lier stages (e.g., fetus) common in mice and humans. Our findings provide a foundation for further genetic studies of cardiomyocyte maturation.     

The Methodology Used to Measure Differential Gene Expression Affects the Outcome

Confirmation of gene expression by a second methodology is critical in order to detect false-positive findings associated with microarrays. However, the impact of methodology upon the measurement of gene expression has not been rigorously evaluated. In the current study, we compared differential gene expression between PC3 and PC3-M human prostate cancer cell lines using three separate methods: microarray, quantitative RT/PCR (qRT/PCR), and Northern blotting. The PC3 to PC3-M ratio of gene expression was determined for each of 24 different genes evaluated, by each of the three methods. Comparison of gene expression ratios between Northern and microarray, Northern and qRT/PCR, and microarray and qRT/PCR, gave correlation coefficients (r) of 0.72, 0.39, and 0.63, respectively. In each instance, one to two outlier genes were apparent. Their exclusion from analysis gave r values of 0.79, 0.72, and 0.83, respectively. These findings demonstrate that the assessment of differential gene expression is dependent upon the methodology used in each situation where outcome between different methodologies was compared, the presence of a relatively limited number of outlier genes precludes high overall correlation between the methods. Validation of gene expression by different methods should be performed whenever possible.     

6天龄与10天龄大鼠的睾丸组织的基因差异表达

通过基因芯片技术,利用Roche-NimbleGen公司制作的大鼠12×135K全基因组表达谱芯片,对日龄为6d和10d的大鼠睾丸组织进行全基因组表达差异分析。结果显示:具有2倍以上的差异表达基因有4298个,其中表达上调的基因共1878个,表达下调的基因共2420个。这些差异表达的基因中有3154个基因具有基因本体注释,参与了154个生物学通路。进一步分析表明具有8倍以上差异表达的基因有13个,这些基因参与了生物学过程、细胞组分和分子功能等基因本体分类,进一步选择3个差异表达的基因,LOC686076、Cxcl6和Trib3,做了实时定量RT-PCR检测。其结果趋势与芯片数据一致。因此,我们初步认为精原干细胞的发生与增殖在大鼠早期的发育过程中已经有大量的基因参与,是一个多基因协调表达的过程。