Dataset Information

Spatial distribution of marker gene activity in the mouse lung during alveolarization.

ABSTRACT: This data is a curated collection of visual images of gene expression patterns from the pre- and post-natal mouse lung, accompanied by associated mRNA probe sequences and RNA-Seq expression profiles. Mammalian lungs undergo significant growth and cellular differentiation before and after the transition to breathing air. Documenting normal lung development is an important step in understanding abnormal lung development, as well as the challenges faced during a preterm birth. Images in this dataset indicate the spatial distribution of mRNA transcripts for over 500 different genes that are active during lung development, as initially determined via RNA-Seq. Images were systematically acquired using high-throughput in situ hybridization with non-radioactive digoxigenin-labeled mRNA probes across mouse lungs from developmental time points E16.5, E18.5, P7, and P28. The dataset was produced as part of The Molecular Atlas of Lung Development Program (LungMAP) and is hosted at https://lungmap.net. This manuscript describes the nature of the data and the protocols for generating the dataset.

SUBMITTER: Ljungberg MC

PROVIDER: S-EPMC6307338 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Spatial distribution of marker gene activity in the mouse lung during alveolarization.

Ljungberg M Cecilia MC Sadi Mayce M Wang Yunguan Y Aronow Bruce J BJ Xu Yan Y Kao Rong J RJ Liu Ying Y Gaddis Nathan N Ardini-Poleske Maryanne E ME Umrod Tipparat T Ambalavanan Namasivayam N Nicola Teodora T Kaminski Naftali N Ahangari Farida F Sontag Ryan R Corley Richard A RA Ansong Charles C Carson James P JP

Data in brief 20181103

This data is a curated collection of visual images of gene expression patterns from the pre- and post-natal mouse lung, accompanied by associated mRNA probe sequences and RNA-Seq expression profiles. Mammalian lungs undergo significant growth and cellular differentiation before and after the transition to breathing air. Documenting normal lung development is an important step in understanding abnormal lung development, as well as the challenges faced during a preterm birth. Images in this datase ...[more]

PMID: 30596133

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Project description:Lung development occurs under relative hypoxia and the most important oxygen-sensitive response pathway is driven by Hypoxia Inducible Factors (HIF). HIFs are heterodimeric transcription factors of an oxygen-sensitive subunit, HIF?, and a constitutively expressed subunit, HIF1?. HIF1? and HIF2?, encoded by two separate genes, contribute to the activation of hypoxia inducible genes. A third HIF? gene, HIF3?, is subject to alternative promoter usage and splicing, leading to three major isoforms, HIF3?, NEPAS and IPAS. HIF3? gene products add to the complexity of the hypoxia response as they function as dominant negative inhibitors (IPAS) or weak transcriptional activators (HIF3?/NEPAS). Previously, we and others have shown the importance of the Hif1? and Hif2? factors in lung development, and here we investigated the role of Hif3? during pulmonary development. Therefore, HIF3? was conditionally expressed in airway epithelial cells during gestation and although HIF3? transgenic mice were born alive and appeared normal, their lungs showed clear abnormalities, including a post-pseudoglandular branching defect and a decreased number of alveoli. The HIF3? expressing lungs displayed reduced numbers of Clara cells, alveolar epithelial type I and type II cells. As a result of HIF3? expression, the level of Hif2? was reduced, but that of Hif1? was not affected. Two regulatory genes, Rar?, involved in alveologenesis, and Foxp2, a transcriptional repressor of the Clara cell specific Ccsp gene, were significantly upregulated in the HIF3? expressing lungs. In addition, aberrant basal cells were observed distally as determined by the expression of Sox2 and p63. We show that Hif3? binds a conserved HRE site in the Sox2 promoter and weakly transactivated a reporter construct containing the Sox2 promoter region. Moreover, Hif3? affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel function of Hif3? beyond the hypoxia response.

Dataset Information

Spatial distribution of marker gene activity in the mouse lung during alveolarization.

Publications

Spatial distribution of marker gene activity in the mouse lung during alveolarization.

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