Dataset Information

Maternally imprinted microRNAs are differentially expressed during mouse and human lung development.

ABSTRACT: MicroRNAs (miRNAs) are a recently discovered class of noncoding genes that regulate the translation of target mRNA. More than 300 miRNAs have now been discovered in humans, although the function of most is still unknown. A highly sensitive, semiquantitative real-time polymerase chain reaction method was used to reveal the differential expression of several miRNAs during the development of both mouse and human lung. Of note was the up-regulation in neonatal mouse and fetal human lung of a maternally imprinted miRNA cluster located at human chromosome 14q32.31 (mouse chromosome 12F2), which includes the miR-154 and miR-335 families and is situated within the Gtl2-Dio3 domain. Conversely, several miRNAs were up-regulated in adult compared with neonatal/fetal lung, including miR-29a and miR-29b. Differences in the spatial expression patterns of miR-154, miR-29a, and miR-26a was demonstrated using in situ hybridization of mouse neonatal and adult tissue using miRNA-specific locked nucleic acid (LNA) probes. Of interest, miR-154 appeared to be localized to the stroma of fetal but not adult lungs. The overall expression profile was similar for mouse and human tissue, suggesting evolutionary conservation of miRNA expression during lung development and demonstrating the importance of maternally imprinted miRNAs in the developmental process.

SUBMITTER: Williams AE

PROVIDER: S-EPMC2582151 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Maternally imprinted microRNAs are differentially expressed during mouse and human lung development.

Williams Andrew E AE Moschos Sterghios A SA Perry Mark M MM Barnes Peter J PJ Lindsay Mark A MA

Developmental dynamics : an official publication of the American Association of Anatomists 20070201 2

MicroRNAs (miRNAs) are a recently discovered class of noncoding genes that regulate the translation of target mRNA. More than 300 miRNAs have now been discovered in humans, although the function of most is still unknown. A highly sensitive, semiquantitative real-time polymerase chain reaction method was used to reveal the differential expression of several miRNAs during the development of both mouse and human lung. Of note was the up-regulation in neonatal mouse and fetal human lung of a materna ...[more]

PMID: 17191223

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Project description:BackgroundRecent meta-analyses of genome-wide association studies have identified single nucleotide polymorphisms (SNPs) within/near 54 genes associated with lung function measures. Current understanding of the contribution of these genes to human lung development is limited. We set out to further define i) the expression profile of these genes during human lung development using a unique set of resources to examine both mRNA and protein expression and ii) the link between key polymorphisms and genes using expression quantitative trait loci (eQTL) approaches.MethodsThe mRNA expression profile of lung function associated genes across pseudoglandular and canalicular stages of lung development were determined using expression array data of 38 human fetal lungs. eQTLs were investigated for selected genes using blood cell and lung tissue data. Immunohistochemistry of the top 5 candidates was performed in a panel of 24 fetal lung samples.ResultsTwenty-nine lung function associated genes were differentially expressed during lung development at the mRNA level. The greatest magnitude of effect was observed for 5 genes; TMEM163, FAM13A and HHIP which had increasing expression and CDC123 and PTCH1 with decreased expression across developmental stages. Focussed eQTL analyses investigating SNPs in these five loci identified several cis-eQTL's. Protein expression of TMEM163 increased and CDC123 decreased with fetal lung age in agreement with mRNA data. Protein expression in FAM13A, HHIP and PTCH1 remained relatively constant throughout lung development.ConclusionsWe have identified that > 50 % of lung function associated genes show evidence of differential expression during lung development and we show that in particular TMEM163 and CDC123 are differentially expressed at both the mRNA and protein levels. Our data provides a systematic evaluation of lung function associated genes in this context and offers some insight into the potential role of several of these genes in contributing to human lung development.

Dataset Information

Maternally imprinted microRNAs are differentially expressed during mouse and human lung development.

Publications

Maternally imprinted microRNAs are differentially expressed during mouse and human lung development.

Similar Datasets

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