Expression Profiles of the Mouse Lung Identify a Molecular Signature of Time-to-Birth

Kho, Alvin T.; Bhattacharya, Soumyaroop; Mecham, Brigham H.; Hong, Jin; Kohane, Isaac S.; Mariani, Thomas J.

doi:10.1165/rcmb.2008-0048oc

Cited by 41 publications

(60 citation statements)

References 50 publications

(55 reference statements)

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“…1 a k,n *g n , where the magnitude of the loading coefficient (a k,j ) indicates the contribution of g j in PCk. We define the "characteristic genes" of a PC as the probes/genes with the top 5% loading coefficient magnitudes (6,17), or the probes/genes with loading coefficient magnitude greater than 0.01 of that PC.…”

Section: Pcamentioning

confidence: 99%

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Kho

Chhabra

Sharma

et al. 2016

Am J Respir Cell Mol Biol

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The fetal origins of disease hypothesis suggests that variations in the course of prenatal lung development may affect life-long pulmonary function growth, decline, and pathobiology. Many studies support the existence of differences in the developing lung trajectory in males and females, and sex-specific differences in the prevalence of chronic lung diseases, such as asthma and bronchopulmonary dysplasia. The objectives of this study were to investigate the early developing fetal lung for transcriptomic correlates of postconception age (maturity) and sex, and their associations with chronic lung diseases. We analyzed whole-lung transcriptome profiles of 61 females and 78 males at 54-127 days postconception (dpc) from nonsmoking mothers using unsupervised principal component analysis and supervised linear regression models. We identified dominant transcriptomic correlates for postconception age and sex with corresponding gene sets that were enriched for developing lung structural and functional ontologies. We observed that the transcriptomic sex difference was not a uniform global time shift/lag, rather, lungs of males appear to be more mature than those of females before 96 dpc, and females appear to be more mature than males after 96 dpc. The age correlate gene set was consistently enriched for asthma and bronchopulmonary dysplasia genes, but the sex correlate gene sets were not. Despite sex differences in the developing fetal lung transcriptome, postconception age appears to be more dominant than sex in the effect of early fetal lung developments on disease risk during this early pseudoglandular phase of development.

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Section: Pcamentioning

confidence: 99%

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Kho

Chhabra

Sharma

et al. 2016

Am J Respir Cell Mol Biol

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“…Mean gene expression for each group was compared with two previously published data sets of whole lung gene expression over the course of lung development (24,26). Gene mapping from mouse to human was based on MGD Vertebrate Homology table (27).…”

Section: Mouse Lung Development Benchmarkingmentioning

confidence: 99%

Excessive Reversal of Epidermal Growth Factor Receptor and Ephrin Signaling Following Tracheal Occlusion in Rabbit Model of congenital Diaphragmatic Hernia

Varisco

Sbragia

Chen

et al. 2016

Mol Med

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“…Differential expression was defined in the full transcriptome of 54,675 probe sets using Significance Analysis of Microarrays (25) at a median FDR 5 0 in TIGR Multi-experiment Viewer (http://www.tm4.org/ mev.html) as we have previously described (18). Genes were further restricted to those demonstrating a fold change of 2.0 or greater in average expression.…”

Section: Differential Expression Analysis Of Array Datamentioning

confidence: 99%

“…Recently, high-throughput technologies (e.g., microarrays) have enabled comprehensive studies of genome-wide expression patterns and global biological processes underlying organogenesis of the mouse lung (16)(17)(18). Related studies of abnormal lung development in the mouse suggest the existence of essential regulatory modules that recur throughout development and transcend histomorphologic compartmentalization (19)(20)(21)(22).…”

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Transcriptomic Analysis of Human Lung Development

Kho

Bhattacharya

Tantisira

et al. 2010

Am J Respir Crit Care Med

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109

110

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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.

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Expression Profiles of the Mouse Lung Identify a Molecular Signature of Time-to-Birth

Cited by 41 publications

References 50 publications

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Excessive Reversal of Epidermal Growth Factor Receptor and Ephrin Signaling Following Tracheal Occlusion in Rabbit Model of congenital Diaphragmatic Hernia

Transcriptomic Analysis of Human Lung Development

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