Update on Molecular Biology of Lung Development—Transcriptomics

Mariani, Thomas J.

doi:10.1016/j.clp.2015.08.001

Cited by 8 publications

(6 citation statements)

References 56 publications

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“…We also tested different culture media compositions in an effort to expand and differentiate PHLE cells, with the intention of generating ALI cultures with distinct proximal versus distal phenotypes. Others have demonstrated growth of ATII-like cells from fetal lungs (9, 35) and adult lungs cells (36). We used three different media: SAGM+1%FBS (36), DMEM with KGF, Dexamethasone, IBMX and cAMP supplement (KDCI) (35) and Waymouth’s media with DCI (9, 37).…”

Section: Discussionmentioning

confidence: 99%

“…Others have demonstrated growth of ATII-like cells from fetal lungs (9, 35) and adult lungs cells (36). We used three different media: SAGM+1%FBS (36), DMEM with KGF, Dexamethasone, IBMX and cAMP supplement (KDCI) (35) and Waymouth’s media with DCI (9, 37). However, PHLE cells showed poor growth characteristics and failed to maintain transepithelial resistance when grown under conditions promoting distal/alveolar cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

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A novel in vitro model of primary human pediatric lung epithelial cells

et al. 2019

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Background: Current in vitro human lung epithelial cell models derived from adult tissues may not accurately represent all attributes that define homeostatic and disease mechanisms relevant to the pediatric lung. Methods: We report methods for growing and differentiating primary Pediatric Human Lung Epithelial (PHLE) cells from organ donor infant lung tissues. We use immunohistochemistry, flow cytometry, quantitative RT-PCR, and single cell RNA sequencing (scRNAseq) analysis to characterize the cellular and transcriptional heterogeneity of PHLE cells. Results: PHLE cells can be expanded in culture up to passage 6, with a doubling time of approximately 4 days, and retain attributes of highly enriched epithelial cells. PHLE cells can form resistant monolayers, and undergo differentiation when placed at air-liquid interface. When grown at Air-Liquid Interface (ALI), PHLE cells expressed markers of airway epithelial cell lineages. scRNAseq suggests the cultures contained 4 main sub-phenotypes defined by expression of FOXJ1, KRT5, MUC5B and SFTPB. These cells are available to the research community through the Developing Lung Molecular Atlas Program Human Tissue Core. Conclusion: Our data demonstrate that PHLE cells provide a novel in vitro human cell model that represents the pediatric airway epithelium, which can be used to study perinatal developmental and pediatric disease mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A novel in vitro model of primary human pediatric lung epithelial cells

et al. 2019

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“…To this end, a large number of transcriptomic studies have been undertaken, addressing changes in mRNA and microRNA expression 159–161 , and these data are only now being interrogated and explored. An integrated systems-biology approach will reveal new, or confirm suspected mechanisms that misdirect lung development in BPD patients, or in experimental animal models of BPD.…”

Section: Understanding Bpd Pathobiology – Future Directionsmentioning

confidence: 99%

Can We Understand the Pathobiology of Bronchopulmonary Dysplasia?

Alvira

Morty

2017

The Journal of Pediatrics

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“…Studies on alveolarization generally rely on the identification and validation of pathways that direct lung development, using pharmacological and genetic approaches. Small‐molecule and proteinaceous modulators of developmental pathways have been administered via the enteral or parenteral routes, and subsequently, the impact on the development of the lung structure might be assessed microscopically (Valenzuela et al, ) or radiologically (Xiao et al, ); alongside screens for transcriptomic changes (Mariani, ), by microarray, or more recently, RNA‐Seq (Bhattacharya et al, ; Lingappan et al, ) technology. Small‐molecule interventions have, in the past, relied on enzyme inhibitors to block enzyme function (Reviewed in Madurga et al, ; Silva et al, ; Surate Solaligue et al, ); but have recently been expanded to include chemical chaperones (Nguyen and Uhal, ; Siddesha et al, ) and genetic interference, through sequence‐specific modulation of microRNA function using antagomiRs (Nardiello and Morty, ) or microRNA mimics (Olave et al, ; Durrani‐Kolarik et al, ).…”

mentioning

confidence: 99%

Control Interventions Can Impact Alveolarization and the Transcriptome in Developing Mouse Lungs

Fehl

Pozarska

Nardiello

et al. 2018

The Anatomical Record

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There is currently much interest in understanding the mechanisms of normal and aberrant lung alveolarization, particularly in the context of bronchopulmonary dysplasia, a common complication of preterm birth where alveolarization is impeded. To this end, the parenteral administration of pharmacological agents that modulate biochemical pathways, or facilitate modulation of gene expression in transgenic animals, has facilitated the discovery and validation of mechanisms that direct lung development. Such studies include control interventions, where the solvent vehicle, perhaps containing an inactive form of the agent applied, is administered; thereby providing a well-controlled point of reference for the analysis of the partner experiment. In the present study, the impact of several widely used control interventions in developing C57Bl/6J mouse pups was examined for effects on lung structure and the lung transcriptome. Parenteral administration of scrambled microRNA inhibitors (called antagomiRs) that are used to control in vivo microRNA neutralization studies, impacted lung volume, septal thickness, and the transcriptome of developing mouse lungs; with some effects dependent upon nucleotide sequence. Repeated intraperitoneal isotonic saline injections altered lung volume, with limited impact on the transcriptome. Parenteral administration of the tamoxifen solvent Miglyol accelerated mouse pup growth, and changed the abundance of 73 mRNA transcripts in the lung. Tamoxifen applied in Miglyol-in the absence of Cre recombinase-decreased pup growth, lung volume, and lung alveolarization and changed the abundance of 298 mRNA transcripts in the lung. These data demonstrate that widely used control interventions can directly impact lung alveolarization and the lung transcriptome in studies on lung development.

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Update on Molecular Biology of Lung Development—Transcriptomics

Cited by 8 publications

References 56 publications

A novel in vitro model of primary human pediatric lung epithelial cells

A novel in vitro model of primary human pediatric lung epithelial cells

Can We Understand the Pathobiology of Bronchopulmonary Dysplasia?

Control Interventions Can Impact Alveolarization and the Transcriptome in Developing Mouse Lungs

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