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Human induced pluripotent stem cell-derived vocal fold mucosa mimics development and responses to smoke exposure

ABSTRACT: Human induced pluripotent stem cell-derived vocal fold mucosa mimics development and responses to smoke exposure

PROVIDER: PRJNA559267 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9925410.fastq.gz	Fastqsanger.gz
	SRR9925411.fastq.gz	Fastqsanger.gz
	SRR9925404.fastq.gz	Fastqsanger.gz
	SRR9925405.fastq.gz	Fastqsanger.gz
	SRR9925406.fastq.gz	Fastqsanger.gz

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Human induced pluripotent stem cell-derived vocal fold mucosa mimics development and responses to smoke exposure

Project description:Development of treatments for vocal dysphonia has been inhibited by lack of human vocal fold (VF) mucosa models because of difficulty in procuring VF epithelial cells, epithelial cells’ limited proliferative capacity and absence of cell lines. We report development of engineered VF mucosae from hiPSC, transfected via TALEN constructs for green fluorescent protein, that mimic development of VF epithelial cells in utero. Modulation of FGF signaling achieves stratified squamous epithelium from definitive and anterior foregut derived cultures. Robust culturing of these cells on collagen-fibroblast constructs produces three-dimensional models comparable to in vivo VF mucosa. Second, we demonstrate mucosal inflammation upon exposure of these constructs to 5% cigarette smoke extract. Upregulation of pro-inflammatory genes in epithelium and fibroblasts leads to aberrant VF mucosa remodeling. Collectively, our results demonstrate that hiPSC-derived VF mucosa is a versatile tool for future investigation of genetic and molecular mechanisms underlying epithelium-fibroblasts interactions in health and disease.

2019-08-09 | GSE135548 | GEO

Protein turnover during in vitro human vocal fold mucosa remodeling

Project description:We present here the first study evaluating the dynamic proteome changes in the remodeling process of decellularized tissue by reseeded cells using vocal fold mucosa as the model system.

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Comparative proteomics of paired human vocal fold and oral mucosa tissue

Project description:This dataset brief is about the descriptive proteomic comparison of human oral mucosa and vocal fold tissues by high-resolution mass spectrometry (CID-MS/MS). The vast majority of voice disorders is associated with changes of the unique but delicate tissue of the human vocal folds, wheras the ability to develop new effective treatment methods is significantly limited by the physical inaccessibility and the extremely rare occasion to gather healthy tissue biopsies. Therefore, oral mucosa reached specific interest for laryngological research, as the tissue harvesting process is less invasive and accompanied with faster healing and less scarring. Proteomic analysis of both tissues will provide a fundamental laryngological resource for the research community. Our study identifies a total of 1575 proteins detected within both tissues that are highly consistent in several crucial biological processes, cellular components, and molecular functions.

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Transcription in wounded rat vocal folds and vocal fold fibroblasts

Project description:We used microarrays to characterize transcriptome profiles of rat vocal fold tissue following surgical injury (vs. naive tissue); rat vocal fold fibroblasts harvested from scar tissue at the 60 d time point (vs. naive fibroblasts); rat vocal fold scar fibroblasts treated with siRNA against the collagen chaperone protein rat gp46 (vs. scramble siRNA). Adult Fischer 344 rat vocal fold tissue was harvested at 3, 14, and 60 days following surgical injury (control = age-matched naive tissue); rat vocal fold scar fibroblasts were obtained via explant culture of tissue obtained 60 days following surgical injury and harvested at 80% confluence during passage 1 (control = age-matched naive rat vocal fold fibroblasts); rat vocal fold scar fibroblasts were treated for 1 h with 50 nM liposome-delivered siRNA against rat gp46 when 80% confluent at passage 1, cultured for an additional 24 h in fresh media, then harvested (control = rat vocal fold scar fibroblasts treated with 50 nM liposome-delivered scramble siRNA).

2014-10-09 | E-GEOD-62204 | biostudies-arrayexpress

Expression data from rat vocal fold at different periods after vocal fold injury

Project description:Expression data from rat vocal fold at different periods after vocal fold injury

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Proteomic analysis of vocal fold fibroblasts exposed to cigarette smoke extract

Project description:Reinke’s edema is a cigarette associated, benign, mostly bilateral lesion of the vocal folds leading to dysphonia and dyspnea. Until today information about pathophysiology is only scarce, treatment is only surgical. To explore the pathophysiology of Reinke’s edema, we exposed near primary human vocal fold fibroblasts to cigarette smoke extract enriched medium or air bubbled control for 24 hrs. followed by a proteomic analysis. Proteomic analyses revealed an increase of proteins involved in oxidative stress response. We furthermore found that a significant number of essential extracellular matrix proteins was altered by culturing human VFF with CSE enriched medium: UDP-glucose 6-dehydrogenase, a protein involved in hyaluronan synthesis was upregulated, while the expression of several fibrillar collagen types was significantly reduced. The current findings corroborate previous studies but revealed new insights in possible disease mechanisms of Reinke’s edema too. We postulate that changes in the composition -reduction of collagen fibrils, increase of hyaluronan- of the vocal folds’ ECM may lead to the clinical findings.

2019-08-06 | PXD010640 | Pride

Transcription in wounded rat vocal folds and vocal fold fibroblasts

2014-10-09 | GSE62204 | GEO

Expression data from rat vocal fold at different periods after vocal fold injury (miRNA)

Project description:Expression data from rat vocal fold at different periods after vocal fold injury (miRNA)

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Project description:Injuries of the vocal folds frequently heal with scar formation, which can have lifelong detrimental impact on voice quality. Current treatments to prevent or resolve scars of the vocal fold mucosa are highly unsatisfactory. In contrast, the adjacent oral mucosa is mostly resistant to scarring. These differences in healing tendency might relate to distinct properties of the fibroblasts populating oral and vocal fold mucosae. We thus established the in vitro cultivation of paired, near-primary vocal fold fibroblasts (VFF) and oral mucosa fibroblasts (OMF) to perform a basic cellular characterization and comparative cellular proteomics. VFF were significantly larger than OMF, proliferated more slowly, and exhibited a sustained TGF-β1-induced elevation of pro-fibrotic interleukin 6. Cluster analysis of the proteomic data revealed distinct protein repertoires specific for VFF and OMF. Further, VFF displayed a broader protein spectrum, particularly a more sophisticated array of factors constituting and modifying the extracellular matrix. Conversely, subsets of OMF-enriched proteins were linked to cellular proliferation, nuclear events, and protection against oxidative stress. Altogether, this study supports the notion that fibroblasts sensitively adapt to the functional peculiarities of their respective anatomical location and presents several molecular targets for further investigation in the context of vocal fold wound healing.

2017-01-23 | PXD005106 | Pride

Expression data from rat vocal fold at different periods after vocal fold injury

Project description:Vocal cord healing is a dynamic process, and many genes and proteins are involved, which play varying roles at different regeneration stages after injury. Previous studies have shown that inflammatory responses occur at the early stage of vocal cord injury, where the fibroblasts proliferate exuberantly with intensive secretion and deposition of ECM. These activities reach the peak at 3-7 days and their intensity begins to decline 15 days later. A study based on the dermal system has shown that ECM remodeling during the repair of injury can last for several months. However, few studies have been conducted as to the dynamic changes of gene expressions and signaling pathway during the healing process of vocal cord injury. Plotting these changes will facilitate the understanding about the physiological changes during healing and the identification of key time points and target genes in fibrosis formation.

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