Lonergan Kim M, Chari Raj, Deleeuw Ronald J, Shadeo Ashleen, Chi Bryan, Tsao Ming-Sound, Jones Steven, Marra Marco, Ling Victor, Ng Raymond, Macaulay Calum, Lam Stephen, Lam Wan L
Cancer Genetics and Developmental Biology, Department of Cancer Imaging, Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Am J Respir Cell Mol Biol. 2006 Dec;35(6):651-61. doi: 10.1165/rcmb.2006-0056OC. Epub 2006 Jun 29.
A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases, including cancer. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based on a vast dataset of nearly two million sequence tags from 21 serial analysis of gene expression (SAGE) libraries from individuals with a history of smoking. Our analysis suggests that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. Moreover, our analysis has identified novel bronchial-enriched genes such as MS4A8B, and has demonstrated the use of SAGE for the discovery of novel transcript variants. Significantly, gene expression associated with ciliogenesis is evident in bronchial epithelium, and includes the expression of transcripts specifying axonemal proteins DNAI2, SPAG6, ASP, and FOXJ1 transcription factor. Moreover, expression of potential regulators of ciliogenesis such as MDAC1, NYD-SP29, ARMC3, and ARMC4 were also identified. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, and constitutes one of the largest human SAGE studies reported to date.
对人类支气管上皮转录组的描述应为研究包括癌症在内的肺部疾病提供依据。基于来自有吸烟史个体的21个基因表达序列分析(SAGE)文库中近两百万个序列标签的庞大数据集,我们推导了支气管上皮和肺实质的整体基因表达谱。我们的分析表明,支气管上皮的转录组与肺实质及其他组织类型的转录组不同。此外,我们的分析鉴定出了如MS4A8B等新的支气管富集基因,并证明了SAGE可用于发现新的转录变体。值得注意的是,与纤毛发生相关的基因表达在支气管上皮中很明显,包括指定轴丝蛋白DNAI2、SPAG6、ASP和FOXJ1转录因子的转录本的表达。此外,还鉴定出了纤毛发生潜在调节因子如MDAC1、NYD-SP29、ARMC3和ARMC4的表达。这项研究全面描绘了支气管和实质转录组,鉴定出了在人肺中表达的两万多个已知和假设基因,是迄今为止报道的最大规模的人类SAGE研究之一。