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

Ljungberg, M. Cecilia; Sadi, Mayce; Wang, Yunguan; Aronow, Bruce J.; Xu, Yan; Kao, Rong J.; Liu, Ying; Gaddis, Nathan; Ardini-Poleske, Mary-Anne; Umrod, Tipparat; Ambalavanan, Namasivayam; Nicola, Teodora; Kaminski, Naftali; Ahangari, Farida; Sontag, Ryan; Corley, Richard A.; Ansong, Charles; Carson, James P.

doi:10.1016/j.dib.2018.10.150

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…These observations are consistent with a delay in lung development. Robust Wfdc2 expression is seen throughout lung development [23,49] and this data suggest that the protein functions May 2020 somehow to promote lung development. Roles for WFDC2 outside of the wider respiratory tract remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Expression and function of murine WFDC2 in the respiratory tract

Bingle

Armes

Williams

et al. 2020

Preprint

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WFDC2/HE4 encodes a poorly characterised secretory protein that shares structural similarity with multifunctional host defence proteins through possession of two conserved Whey Acidic Protein/four disulphide-core (WFDC) domains. WFDC2 is expressed in multiple epithelia and although its' function remains unresolved, it is also overexpressed in a number of human cancers and has an established role as a cancer marker. Currently, little is known about the distribution of WFDC2 in the mouse and thus we have systematically analysed the mouse wfdc2 gene, its' expression and distribution. We have used recombinant WFDC2 for functional studies. Wfdc2 is the most highly expressed family member in the lung and is enriched in the nasopharynx. Wfdc2 is the most highly expressed family member in differentiated epithelial cells isolated from the trachea, nasal passages and middle ear. Wfdc2 consists of 5 exons with exon 3 encoding an unstructured linker region that separates the two WFDC domains. This genomic organisation appears to be restricted to the Muridae and Cricetidae families of rodents.Similar to the situation in man, mouse wfdc2 can be alternatively spliced to yield a number of distinct transcripts that have the potential to generate a repertoire of distinct protein isoforms.We used immunohistochemistry to localise the proteins to tissues of the respiratory tract and head and neck regions. Although the protein was limited to epithelial cells of the respiratory tract and nasal and oral cavities, it was expressed in different cells in different regions suggesting expression is governed by a unique regulatory mechanism. Recombinant WFDC2 did not possess antiproteinase activity against trypsin or elastase and had no clear antimicrobial activity.

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Section: Discussionmentioning

confidence: 99%

Expression and function of murine WFDC2 in the respiratory tract

Bingle

Armes

Williams

et al. 2020

Preprint

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“…ST is used to construct lungs spatial atlas and identify cellular composition. In lung cancer, the tumor microenvironment [ 63 ] and heterogeneity [ 64 ], evolution and metastasis [ 65 ], and further localization of intratumoral microbiota origin [ 66 ] have been revealed by ST. Other applications of ST include gene expression patterns in lung development [ 67 ], and the pathogenesis of pulmonary fibrosis [ 68 ] and COVID-19 pneumonia [ 69 ]. ST spatial transcriptomic, COVID-19 corona virus disease 2019, NK cell natural killer cell …”

Section: Applications Of St To Respiratory Researchmentioning

confidence: 99%

“…Ljungberg et al [ 67 ] using spatial in situ hybridization attempted to elucidate gene expression patterns in prenatal and postnatal murine lungs to describe the details of lung development at critical stages of alveolarization and improve data for LungMap. A recent study applied in situ hybridization analysis to determine the origin of clonogenic mesenchymal cells in the human lung, especially from an adventitial fibroblast subset.…”

Section: Applications Of St To Respiratory Researchmentioning

confidence: 99%

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Spatial transcriptomics: recent developments and insights in respiratory research

Wang,

Chu,

et al. 2023

Military Med Res

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The respiratory system’s complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.

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“…Several recent reports have provided valuable reference information for the lung development community, including the spatial description of marker gene activity over the course of alveolarization (340). A comprehensive description of the impact of control interventions (such as saline, tamoxifen, Miglyol, and scrambled microRNA antimiR injections) on the lung transcriptome and development of the lung structure has also been provided (160).…”

Section: Animal Models Of Bpdmentioning

confidence: 99%

Recent advances in our understanding of the mechanisms of lung alveolarization and bronchopulmonary dysplasia

Lignelli

Palumbo

Myti

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

111

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Bronchopulmonary dysplasia (BPD) is the most common cause of morbidity and mortality in preterm infants. A key histopathological feature of BPD is stunted late lung development, where the process of alveolarization—the generation of alveolar gas exchange units—is impeded, through mechanisms that remain largely unclear. As such, there is interest in the clarification both of the pathomechanisms at play in affected lungs, and the mechanisms of de novo alveoli generation in healthy, developing lungs. A better understanding of normal and pathological alveolarization might reveal opportunities for improved medical management of affected infants. Furthermore, disturbances to the alveolar architecture are a key histopathological feature of several adult chronic lung diseases, including emphysema and fibrosis, and it is envisaged that knowledge about the mechanisms of alveologenesis might facilitate regeneration of healthy lung parenchyma in affected patients. To this end, recent efforts have interrogated clinical data, developed new—and refined existing—in vivo and in vitro models of BPD, have applied new microscopic and radiographic approaches, and have developed advanced cell-culture approaches, including organoid generation. Advances have also been made in the development of other methodologies, including single-cell analysis, metabolomics, lipidomics, and proteomics, as well as the generation and use of complex mouse genetics tools. The objective of this review is to present advances made in our understanding of the mechanisms of lung alveolarization and BPD over the period 1 January 2017–30 June 2019, a period that spans the 50th anniversary of the original clinical description of BPD in preterm infants.

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

Cited by 7 publications

References 16 publications

Expression and function of murine WFDC2 in the respiratory tract

Expression and function of murine WFDC2 in the respiratory tract

Spatial transcriptomics: recent developments and insights in respiratory research

Recent advances in our understanding of the mechanisms of lung alveolarization and bronchopulmonary dysplasia

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