Transcriptomic Analysis of Human Lung Development
Transcriptomic Analysis of Human Lung Development
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DOI：
10.1164/rccm.200907-1063oc
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发表时间：
2010-01-01
影响因子：
24.7
通讯作者：
Mariani, Thomas J.
中科院分区：
文献类型：
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作者：
Kho, Alvin T.;Bhattacharya, Soumyaroop;Mariani, Thomas J.
基本原理：目前对肺发育的分子调控的理解是有限的，主要来自动物study.Objectives：To定义全球模式的基因表达在人类肺development.Methods：全基因组表达谱被用来测量来自38个正常人肺组织在53至154天后概念的RNA样本中的肺转录组。主成分分析被用来表征全球表达的变化，并确定基因和生物属性有助于这些变化。通过定量逆转录聚合酶链反应analysis.Measurements和主要结果：基因表达分析确定以前不与肺的发展，如趋化因子免疫过程的属性，个别基因表达模式进行了验证。肺特征属性（例如，表面活性剂功能）在早于预期的年龄观察到。我们定义了一个3,223个基因的肺特征亚转录组，能够描述大部分过程。在基因表达空间，样本形成了一个时间连续的轨迹与过渡点相关的组织学阶段，并建议存在新的分子亚阶段。表面活性剂基因表达的诱导特征为假腺“分子相”转变。个体基因表达模式独立验证。我们预测的年龄独立的人肺转录组档案的中位数绝对误差为5天，支持的数据和建模approach.Conclusions的有效性：这项研究扩展了我们的知识的关键基因表达模式和生物学属性的基础早期人类肺发育过程。这些数据还表明肺发育的分子阶段的存在。
Rationale: Current understanding of the molecular regulation of lung development is limited and derives mostly from animal studies.Objectives: To define global patterns of gene expression during human lung development.Methods: Genome-wide expression profiling was used to measure the developing lung transcriptome in RNA samples derived from 38 normal human lung tissues at 53 to 154 days post conception. Principal component analysis was used to characterize global expression variation and to identify genes and bioontologic attributes contributing to these variations. Individual gene expression patterns were verified by quantitative reverse transcriptase-polymerase chain reaction analysis.Measurements and Main Results: Gene expression analysis identified attributes not previously associated with lung development, such as chemokine-immunologic processes. Lung characteristics attributes (e.g., surfactant function) were observed at an earlier-than-anticipated age. We defined a 3,223 gene developing lung characteristic subtranscriptome capable of describing a majority of the process. In gene expression space, the samples formed a time-contiguous trajectory with transition points correlating with histological stages and suggesting the existence of novel molecular substages. Induction of surfactant gene expression characterized a pseudoglandular "molecular phase" transition. Individual gene expression patterns were independently validated. We predicted the age of independent human lung transcriptome profiles with a median absolute error of 5 days, supporting the validity of the data and modeling approach.Conclusions: This study extends our knowledge of key gene expression patterns and bioontologic attributes underlying early human lung developmental processes. The data also suggest the existence of molecular phases of lung development.