BBS7 -SHH signaling activity regulates primary cilia for periodontal homeostasis
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ABSTRACT:
PROVIDER: PRJNA782351 | ENA |
REPOSITORIES: ENA
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Project description:Purpose : This study was performed to investigate the changes in gene expression in periodontal ligament (PDL) cells between normal occlusal function and hypofunction through RNA sequencing and elucidate the related role in maintaining the PDL homeostasis. Method : Premolars extracted for orthodontic treatment were used. The teeth with occlusal contact for control group (n=17), teeth without occlusal contact for experienment group (n=17). After the PDL cells were isolated from the extracted teeth, differentially expressed gene (DEG) analysis, and real-time PCR were performed to compare the two groups. The effect of Bardet-Biedl syndrome 7 (BBS7) knockdown was evaluated by RT-qPCR, Wound healing assay, and Tubule formation assay. Result : We detected that the expression of BBS7 was downregulated in occlusal hypofunctional PDL through RNA-sequencing. Sonic Hedgehog signaling (Shh) activity was closely associated with BBS7 expression in periodontal ligament cells. In addition, the cell migration and angiogenesis were also suppressed by BBS7 knockdown in vitro. Conclusion : We suggest that BBS7 plays an essential role in maintaining Shh signaling activity for PDL homeostasis.
2021-11-23 | GSE189288 | GEO
Project description: Not available
| S-EPMC8703258 | biostudies-literature
Project description:Parkinson’s disease (PD) as a progressive neurodegenerative disorder arises from multiple genetic and environmental factors. However, underlying pathological mechanisms remain poorly understood. Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic PD (sPD) patients. Alterations in gene expression appear in pathways related to primary cilia (PC). Accordingly, in these hiPSC-derived hNPCs and neurons, we observe a shortening of PC. Additionally, we detect a shortening of PC in PINK1-deficient human cellular and mouse models of familial PD. Furthermore, in sPD models, the shortening of PC is accompanied by an increased SHH signal transduction. Inhibition of this pathway rescues the alterations in PC morphology and mitochondrial dysfunction. Thus, increased SHH activity due to ciliary dysfunction is needed for the development of pathoetiological phenotypes observed in sPD, like mitochondrial dysfunction. In sum, altered PC function is part of early PD pathoetiology and inhibiting the overactive SHH signaling is a potential neuroprotective therapy.
2022-06-23 | GSE176160 | GEO
Project description:The primary cilium, a signaling organelle projecting from the surface of a cell, controls cellular physiology and behavior. The presence or absence of primary cilia is a distinctive feature of a given tumor type; however, whether and how the primary cilium contributes to tumorigenesis is unknown for most tumors. Medulloblastoma (MB) is a common pediatric brain cancer comprising four groups: SHH, WNT, group 3 (G3), and group 4 (G4). From 111 cases of MB, we show that primary cilia are abundant in SHH and WNT MBs but rare in G3 and G4 MBs. Using WNT and G3 MB mouse models, we show that primary cilia promote WNT MB by facilitating translation of mRNA encoding β-catenin, a major oncoprotein driving WNT MB, whereas cilium loss promotes G3 MB by disrupting cell cycle control and destabilizing the genome. Our findings reveal tumor type–specific ciliary functions and underlying molecular mechanisms. Moreover, we expand the function of primary cilia to translation control and reveal a molecular mechanism by which cilia regulate cell cycle progression, providing new frameworks for studying cilia function in normal and pathologic conditions.
2022-07-04 | GSE207008 | GEO
Project description:Primary cilia and SHH signaling impairments in patient-derived cellular models of Parkinson’s disease
| PRJNA735192 | ENA
Project description: Not available
| S-EPMC2727556 | biostudies-literature
Project description:Astrocyte diversity is greatly influenced by local environmental modulation. In this study, we analyzed how primary ciliary signaling modulates astrocyte subtype-specific maturation and accessed the impact of ciliary deficient astrocytes on neuronal programs and behaviours. Comparative single-cell transcriptomics revealed that primary cilia mediate canonical Shh signaling to modulate astrocyte subtype-specific core features in synaptic regulation, intracellular transport, energy and metabolism. Our results uncover a critical role for primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing brain.
2024-01-24 | GSE253640 | GEO
Project description:Background: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting cilia length must exceed the 6 -7 μm airway surface fluid depth to generate force in the mucus layer, we hypothesized cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers. Methodology/Principal Findings: Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced 15% compared to nonsmokers (p<0.05). In 47 air-dried samples of airway epithelial cells, smoker cilia length was reduced 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 17 samples, smoker cilia length was reduced 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Conclusions/significance: Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia plays a significant role in the pathogenesis of smoking-induced lung disease.
2012-12-13 | E-GEOD-16696 | biostudies-arrayexpress
Project description:Periodontitis can impair the osteogenic differentiation of human periodontal mesenchymal stem cells, but the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles under both physiologic and pathological conditions. We performed comprehensive lncRNAs profiling by lncRNA microarray to identify differentially expressed long noncoding RNA expression between Periodontal ligament stem cells from healthy Periodontal tissue and periodontal ligament stem cells from inflammatory periodontal tissue. Our analysis identified 233 lncRNAs and 423 mRNAs that were differently expressed (fold change >2.0, p-value < 0.05) between the two groups of cells. The GO analysis revealed that the significantly down-regulated biological processes included multicellular organismal process, developmental process and multicellular organismal development and the significantly up-regulated biological processes included cellular process, biological regulation and response to stimulus in periodontal ligament stem cells from inflammatory periodontal tissue. The Pathway analysis revealed that the differentially expressed mRNAs may involved in Focal adhesion, ECM-receptor interaction, Bacterial invasion of epithelial cells, Long-term depression, Circadian entrainment and HIF-1 signaling pathway. Two-condition experiment, periodontal ligament stem cells from healthy periodontal tissue (hPDLSCs) vs. periodontal ligament stem cells from inflammatory periodontal tissue (pPDLSCs), Biological replicates: 3 control replicates (hPDLSCs), 3 testing replicates (pPDLSCs).
2016-02-19 | E-GEOD-78074 | biostudies-arrayexpress
Project description:Sporadic Parkinson’s Disease (sPD) is a progressive neurodegenerative disorder caused by a combination of genetic and environmental factors, however, the etiology remains largely elusive. Here, we used human iPSCs from late onset sPD patients, which were cultivated in vitro for up to 60 passages and screened for known PD associated alterations. Following long-term in vitro cultivation, exclusively neural cells derived from sPD patients developed a reduced mitochondrial respiration and glucose consumption reflecting a sPD specific state of hypometabolism. Integrated analysis of transcriptome, proteome and non-targeted metabolome data identified the citric acid cycle as being the bottleneck in sPD metabolism. A 13C metabolic flux analysis further unraveled the α-ketoglutarate dehydrogenase complex as being central for a reduced flux through the citric acid cycle. This resulted in a substrate availability problem for the electron transport chain and thus a reduced mitochondrial ATP production. Notably, this alterations in basal cellular metabolism were introduced by altered SHH signal transduction due to dysfunctional primary cilia. Upon inhibiting the enhanced SHH signal transduction in sPD, glucose uptake and the activity of the α-ketoglutarate dehydrogenase complex could be restored. Thus, inhibiting overactive SHH signaling maybe a potential neuroprotective therapy for sPD.
2023-10-05 | PXD038399 | Pride