Perturbation of the circadian clock contributes to radiotherapy-induced salivary gland hypofunction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA983230 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24911681_1.fastq.gz | Fastqsanger.gz | |||
| SRR24911681_2.fastq.gz | Fastqsanger.gz | |||
| SRR24911682_1.fastq.gz | Fastqsanger.gz | |||
| SRR24911682_2.fastq.gz | Fastqsanger.gz | |||
| SRR24911683_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 32 |
Similar Datasets
Project description:Salivary gland hypofunction is a common adverse effect during and after radiotherapy of head and neck cancers, resulting in the dry mouth syndrome called xerostomia. Previous studies suggested that the functionality of the salivary gland is under the regulation of the circadian clock, however, the extent and scope of this regulation remains unexplored. Here, we profiled the diurnal fluctuation of gene expression in the mouse submandibular salivary gland. We further analyzed the regulatory role of key circadian transcription factors Bmal1, Nr1d1 (Rev-erba), and Dbp, which revealed a wide range of potential down-stream target genes. The circadian clock was disrupted upon irradiation, as revealed by gene expression analysis. We propose that the mechanism of salivary gland hypofunction in radiotherapy involves perturbation of the circadian clock.
2024-01-01 | GSE234789 | GEO
Project description:Ionizing radiation (IR) – induced salivary gland damage is a common adverse effect in radiotherapy for patients with head and neck cancers. Currently, there is no effective treatment for the resulting salivary gland hypofunction and xerostomia (dry mouth). Here we profiled the acute gene expression change in the mouse submandibular salivary gland, and defined its damage response patterns at the transcriptome level.
2021-09-23 | GSE184673 | GEO
Project description:Objectives: Salivary glands are affected during radiotherapy in the head and neck region, leading to a reduction in salivary flow and changes its composition. Besides negatively affecting the oral soft tissues, this can also lead to dental impairment. Thus, we evaluated the effect of radiotherapy in the proteomic profile of the saliva in patients with head-and-neck-cancer (HNC). Materials and methods: HNC patients had their saliva collected before (BRT), during (2-5 weeks; DRT) and after (3-4 months; ART) radiotherapy. Saliva was also collected from healthy volunteers (control; C). Samples were processed for proteomic analysis. Results: In total 1.055 proteins were identified, among which 46 were common to all groups, while 86, 86, 286 and 395 were exclusively found in C, BRT, DRT and ART, respectively. Remarkably, alpha-enolase was increased 35-fold DRT compared with BRT, while proline-rich proteins were decreased. ART there was a 16-fold increase in scaffold attachment factor-B1 and a 3-fold decrease in alpha-enolase and several cystatins. When compared with C, salivary proteins of BRT patients showed increases cystatin-C, lysozyme C, histatin-1 and proline-rich proteins. Conclusion/Clinical revelance: Both HNC and radiotherapy remarkably change the salivary protein composition. Altogether, our results, for the first time, suggest investigating alpha-enolase levels in saliva DRT in future studies as a possible biomarker and strategy to predict the efficiency of the treatment. Moreover, our data provide important insights for designing dental products that are more effective for these patients and contribute to a better understanding of the progressive changes in salivary proteins induced by radiotherapy.
2021-10-12 | PXD028594 | Pride
Project description:Radiotherapy of head and neck cancer is accompanied by unavoidable co-irradiation of the salivary gland, often resulting in hyposalivation and reduced quality of life. Irradiated salivary gland tissue is characterized by the presence of cellular senescence, fibrosis, and a chronic inflammatory state changing the cellular microenvironment. These microenvironmental changes may be unfavorable for the regenerative potential of tissue stem cells inhibiting regenerative medicine options. Therefore, we investigated microenvironmental changes of the irradiated murine salivary gland and their effect on the potency of salivary gland stem/progenitor cells (SGSCs). After 15 Gy local irradiation of murine salivary glands, alongside an in time advancing decline in function, the submandibular gland (SMG) showed extensive fibrosis, p21-expressing senescent cells, and immune cell infiltration, all indicative of microenvironmental changes. Additionally, irradiated SMG contained a lower number of CD24++/CD29++ and CD24++/CD29+ stem/progenitor cell enrichment marker-expressing cells 30 days post-irradiation which coincides with a reduction in salisphere formation potential over time. However, after subsequent passaging of organoids derived from glands obtained 14 days after irradiation, and to a lesser extent at 30 days post-irradiation, the ability to form secondary organoids recovered to control levels. In contrast, cells obtained from glands at 90, 180, and 360 days post-irradiation irreversibly lost their ability to form organoids, indicating a time-dependent loss of regenerative potential. Transcriptomic analysis showed overexpression of Bmp4 in day 90 organoids derived from irradiated glands compared to the ones from day 14. Inhibition of Bmp4 using Noggin reversed this adverse response suggesting an important role in modulating SGSC function. Thus, early after irradiation, the regenerative potential of surviving SGSCs is preserved and comparable to that of unirradiated cells. At later time points after irradiation, SGSCs lose their regenerative potential suggesting that the prolonged exposure to a deleterious microenvironment leads to an irreversible decline in stemness. Modulation of Bmp4 signaling pathway might improve the regenerative potential of surviving SGSCs and enhance the efficiency of stem cell therapy in restoring the functionality of irradiated salivary glands.
2022-07-21 | GSE208387 | GEO
Project description:Salivary glands that produce and secret saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we established long-term murine salivary gland organoids from 3 major salivary glands, including parotid gland (PG), submandibular gland (SMG), and sublingual gland (SLG). Murine salivary gland organoids expressed gland-specific genes and proteins of acinar, myoepithelial, and duct cells. Organoids were maintained in growth media (named GEM) and further underwent differentiation in differentiation media (named DAM). Our study will provide an experimental platform for the exploration of mechanisms involvled in tissue regeneration, development, or several salivary gland diseases.
2022-05-05 | GSE184091 | GEO
Project description:Effect of miRNAs from CD9+ EVs in salivary gland epithelail cell for anti-fibrotic regeneration in obstructive sialadenitis.
2025-02-18 | GSE233238 | GEO
Project description:Loss of Irf6 leads to disruption of branching morphogenesis and secretory acnii formation in salivary gland. To determine the differentially expressed genes in Irf6 mutant, embryonic salivary gland tissues were extracted at E14.5.
2017-07-29 | GSE102020 | GEO
Project description:Tumors of the major and minor salivary gland encompass a diverse spectrum of diagnostically challenging neoplasms. Recent studies have identified several gene fusions and somatic mutations that are specific or highly enriched in certain salivary gland tumor entities and can assist histopathological diagnosis. Still, there is an unmet need to identify additional diagnostic biomarkers for entities lacking specific alterations. In this study, we collected a comprehensive cohort of 363 cases encompassing 20 different salivary gland tumor entities and explored the potential of DNA methylation to classify these tumors. We were able to show that most entities show specific epigenetic signatures and present a machine learning algorithm that can be used to classify diagnostically challenging cases.
2024-08-31 | GSE243075 | GEO
Project description:Human salivary gland organoids have opened tremendous possibilities for regenerative medicine in patients undergoing radiotherapy for the treatment of head and neck cancer. However, their clinical translation is greatly limited by the current use of Matrigel for organoid derivation and expansion. Here, we envisage that the use of a fully, synthetic hydrogel based on the oligo(-ethylene glycol) functionalized polymer polyisocyanopeptides (PICs) can provide an environment suitable for the generation and expansion of salivary gland organoids (SGOs) after optimization of PIC polymer properties. We demonstrate that PIC hydrogels decorated with the cell-binding peptide RGD allow SGO formation from salivary gland (SG)-derived stem cells. This self-renewal potential is preserved for only 4 passages. It was found that SGOs differentiated prematurely in PIC hydrogels affecting their self-renewal capacity. Similarly, SGOs show decreased expression of immediate early genes (IEGs) after culture in PIC hydrogels. Activation of multiple signalling pathways involved in IEG expression by β-adrenergic agonist isoproterenol, led to increased stem cell self-renewal capacity as measured by organoid forming efficiency (OFE). These results indicate that PIC hydrogels are promising 3D matrices for SGOs, with the option to be used clinically, after further optimization of the hydrogel and culture conditions.
2022-12-10 | GSE220084 | GEO
Project description:modENCODE_submission_722 This submission comes from a modENCODE project of David MacAlpine. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: Most terminally differentiated Drosophila tissues are either polyploid or polytene. Unlike normal chromosomes, where the entire chromosome must be replicated exactly once, polytene chromosomes are often differentially replicated with many regions underreplicated and some overreplicated. We will characterize five different polytene tissues using comparative genomic hybridization (CGH) to identify differentially replicated regions of each chromosome. These studies will also identify tissue specific amplicons, where the replication mediated amplification of specific loci is essential for up-regulation of mRNA levels encoding proteins critical for development. The differential replication of polytene chromosomes in Drosophila will provide a unique opportunity to understand how developmental cues and chromosomal domains influence replication initiation. Keywords: CGH For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CGH. BIOLOGICAL SOURCE 1: Strain: Oregon-R Orr-Weaver; Developmental Stage: Embryo 0-4h; Genotype: TBA; Sex: Unknown; BIOLOGICAL SOURCE 2: Strain: Oregon-R Orr-Weaver; Tissue: larval salivary gland; Genotype: TBA; Sex: Unknown; NUMBER OF REPLICATES: 2; EXPERIMENTAL FACTORS: Tissue larval salivary gland
2010-05-15 | E-GEOD-17289 | biostudies-arrayexpress