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Transcriptomic analysis of human lung development.

ABSTRACT: Current understanding of the molecular regulation of lung development is limited and derives mostly from animal studies.To define global patterns of gene expression during human lung development.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.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.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.

SUBMITTER: Kho AT

PROVIDER: S-EPMC2797628 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Transcriptomic analysis of human lung development.

Kho Alvin T AT Bhattacharya Soumyaroop S Tantisira Kelan G KG Carey Vincent J VJ Gaedigk Roger R Leeder J Steven JS Kohane Isaac S IS Weiss Scott T ST Mariani Thomas J TJ

American journal of respiratory and critical care medicine 20091008 1

<h4>Rationale</h4>Current understanding of the molecular regulation of lung development is limited and derives mostly from animal studies.<h4>Objectives</h4>To define global patterns of gene expression during human lung development.<h4>Methods</h4>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 v ...[more]

PMID: 19815808

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Project description:Background: Epidemiological and clinical evidence points cancer comorbidity with pulmonary chronic disease. The acquisition of some hallmarks of cancer by cells affected with lung pathologies as a cell adaptive mechanism to a shear stress, suggests that could be associated with the establishment of tumoral processes. Objective: To propose a bioinformatic pipeline for the identification of all deregulated genes and the transcriptional regulators (TFs) that are coexpressed during lung cancer establishment, and therefore could be important for the acquisition of the hallmarks of cancer. Methods: Ten microarray datasets (six of lung cancer, four of lung diseases) comparing normal and diseases-related lung tissue were selected to identify hub differentiated expressed genes (DEGs) in common between lung pathologies and lung cancer, along with transcriptional regulators through the utilization of specialized libraries from R language. DAVID bioinformatics tool for gene enrichment analyses was used to identify genes with experimental evidence associated to tumoral processes and signaling pathways. Coexpression networks of DEGs and TFs in lung cancer establishment were created with Coexnet library, and a survival analysis of the main hub genes was made. Results: Two hundred ten DEGs were identified in common between lung cancer and other lung diseases related to the acquisition of tumoral characteristics, which are coexpressed in a lung cancer network with TFs, suggesting that could be related to the establishment of the tumoral pathology in lung. The comparison of the coexpression networks of lung cancer and other lung diseases allowed the identification of common connectivity patterns (CCPs) with DEGs and TFs correlated to important tumoral processes and signaling pathways, that haven´t been studied to experimentally validate their role in the early stages of lung cancer. Some of the TFs identified showed a correlation between its expression levels and the survival of lung cancer patients. Conclusion: Our findings indicate that lung diseases share genes with lung cancer which are coexpressed in lung cancer, and might be able to explain the epidemiological observations that point to direct and inverse comorbid associations between some chronic lung diseases and lung cancer and represent a complex transcriptomic scenario.

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Transcriptomic analysis of human lung development.

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Transcriptomic analysis of human lung development.

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