Cholangiocyte Ciliary Defects Induce Sustained Epidermal Growth Factor Receptor Signaling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1157847 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30574904_1.fastq.gz | Fastqsanger.gz | |||
| SRR30574904_2.fastq.gz | Fastqsanger.gz | |||
| SRR30574905_1.fastq.gz | Fastqsanger.gz | |||
| SRR30574905_2.fastq.gz | Fastqsanger.gz | |||
| SRR30574906_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Background & Aims: The primary cilium, an organelle that protrudes from cell surfaces, is essential for sensing extracellular signals. With disturbed cellular communication and chronic liver pathologies, this organelle's dysfunctions have been linked to disorders, including polycystic liver disease (PLD) and Cholangiocarcinoma (CCA). This study aimed to clarify the interaction between primary cilia and the critical regulator of cellular proliferation known as the epidermal growth factor receptor (EGFR) signaling pathway, which has been linked to several clinical conditions. Approach & Results: The study identified abnormal EGFR signaling pathways inside cholangiocytes lacking functioning primary cilia using liver-specific IFT88 knockout mice, a Pkhd1 mutant rat model, and human cell lines with ciliary deficiencies. Cilia-deficient cholangiocytes showed persistent EGFR activation because of impaired receptor degradation, in contrast to their normal counterparts where EGFR localization to cilia promotes appropriate signaling. By using HDAC6 inhibitors to restore primary cilia, EGFR degradation was accelerated, which in turn reduced the maladaptive signaling. Importantly, EGFR was moved to cilia because of experimental intervention with the HDAC6 inhibitor tubastatin A in an orthotopic rat model, along with a reduction in the phosphorylation of ERK. In cholangiocarcinoma and polycystic liver disease cells, concurrent administration of EGFR and HDAC6 inhibitors displayed synergistic anti-proliferative effects that were related to the restoration of functioning primary cilia. Conclusion: The findings of this study shed light on defective ciliary function and robust EGFR signaling with slower receptor turnover. A potential method for treating EGFR-driven pathologies in PLD and CCA is the pharmacological restoration of primary cilia function.
2024-09-11 | GSE276560 | GEO
Project description:Primary ciliary dyskinesia without obvious electron microscopy defects
| PRJNA635175 | ENA
Project description:Primary ciliary dyskinesia without obvious electron microscopy defects
| PRJNA635176 | ENA
Project description:Dysfunction of motile cilia can impair mucociliary clearance in the airway and result in primary ciliary dyskinesia (PCD), a pediatric syndrome characterized by chronic respiratory infection and bronchiectasis, as well as infertility, laterality defects, and occasionally hydrocephalus due to defects in cilia in other organ systems. We have previously shown that mutations in genes encoding components of the ciliary central pair apparatus (CPA) perturb ciliary motility and result in PCD in mouse models. However, little is known about how epithelial cell types in the ciliary microenvironment of the upper airway respond to defects in ciliary motility and mucociliary clearance. In this study, we have used a single-cell RNA sequencing (scRNA-seq) approach to investigate the effects of ciliary dysfunction on the tracheal epithelial cells from mouse models with mutations in CPA genes Cfap221 (also known as Pcdp1), Cfap54, and Spef2. Expected cell types were identified in the tracheal epithelial samples, including basal cells, suprabasal cells, secretory cells, deuterosomal cells, ciliated cells, tuft cells, ionocytes, and neuroendocrine cells, as well as an unidentified cell type that does not express markers of typical airway cells. The deuterosomal cells were found to exist in two states that differ largely in expression of genes involved in differentiation into the ciliated cell type. Differentially expressed genes (DEGs) were identified for each cell type, and functional enrichment analysis revealed a variety of important cellular functions altered in mutant cells. Overlapping DEGs shed light on general cellular responses to cilia dysfunction, while unique DEGs indicate that some responses may be specific to the individual mutation and ciliary defect. These analyses uncover new information about cellular responses to mucociliary clearance defects in the airway and pathogenesis of PCD.
2024-11-14 | GSE254100 | GEO
Project description:Cellular responses in the airway ciliary microenvironment from mouse models of primary ciliary dyskinesia with central pair apparatus defects
| PRJNA1068556 | ENA
Project description:Culture of human cholangiocyte organoids in hydrogels derived from healthy liver extracellular matrix (LECM) extracts prepared from decellularized human livers are evaluated in an effort to establish a platform for production of cholangiocyte organoids for clinical regenerative applications. Human intrahepatic cholangiocyte organoids (ICO) grown in hydrogels made from LECM are compared those grown in mouse tumor derived basement membrane extracts (BME). Culture was performed with amino acids labeled with stable heavy isotopes to enable separation of ECM from the hydrogels from that of the produced by the cells with mass spectrometry (MS). MS data were used to evaluate the protein production of ICO comparing the different hydrogel substrates. The study also contains evaluation of the properties of the hydrogel substrates and focuses on expansion and differentiation of the ICO.
2022-04-13 | PXD028417 | Pride
Project description:Whole genome profiling of histone methylation (H3K4me3, H3K27me3 and RNA Pol II) in Ciliary derived stem/progenitor cells and differentiated cells. In the present study we focus on the cellular differentiation that involves loss of pluripotency and gain of lineage and cell type-specific characteristics and we show developments from adult ciliary derived stem/progenitor cells to differentiated retinal neurons/glial cells of human cadaveric eyes in vitro. Ciliary pigment epithelial cells isolated from human cadaveric eye balls were cultured in the presence of mitogens like Epidermal Growth Factor (EGF) and Fibroblast Growth Factors (FGF) to generate neurospheres (Stem/progenitor population). The generated neurospheres were plated on laminin and poly-D-lysine-coated cover slips in the presence of the Brain derived neurotrophic factor (BDNF), Retinoic acid (RA) and 10% FBS for the differentiation (Retinal neuron/glial cells). Global Methylation patterns of histone H3K4me3, RNA Pol II and H3K27me3 were analysed in the present study. This work would provide an outline of epigenetic modifications in ciliary derived stem/progenitor cells and the progeny that underwent differentiation into retinal neurons/glial cells and present that specific histone methylations are involved in gene expression reprogramming during the process of differentiation.
2016-07-04 | E-GEOD-65268 | biostudies-arrayexpress
Project description:3D cell culture systems (organoids), cultured from extrahepatic bile duct biopsies, resemble biliary epthelium (cholangiocytes) upon culture according to the protocol previously established for culturing intrahepatic cholangiocyte organoids from liver biopsies (Huch et al. Cell 2015). These extrahepatic cholangiocyte organoids (ECOs) in Canonical-Wnt culture conditions maintain their genetic stability, and transcription profile and can be maintained and propagated during long periods of culturing while still maintaining their functional properties. The data presented in this ArrayExpress submission contained micro array results of 3 different ECO lines that were analyzed for their functional cholangiocyte ion-channels, involved in secreting a protective bicarbonate layer. It was shown that these data closely resemble the expression profile of intrahepatic cholangiocyte organoids (ICOs) as described by our group. Results of the ICOs are deposited in the EMBL-EBI ArrayExpress repository under number E-MTAB-9044.
2021-01-01 | E-MTAB-9807 | biostudies-arrayexpress
Project description:3D cell culture systems (organoids), cultured from liver biopsies, resemble biliary epthelium (cholangiocytes) upon culture. These intrahepatic cholangiocyte organoids (ICOs) maintain their gentic stability, transcription profile and can be maintained propagated during long periods of culturing while still maintaining their functional properties. The data presented in this ArrayExpress submission contained micro array results of 6 from 15 different ICO lines that were analyzed for their functional cholangiocyte ion-channels, involved in secreting a protective bicarbonate layer. It was shown that these data closely resemble the expression profiles of extrahepatic cholangiocyte organoids (ECOs), previously described by Sampaziotis et al. and deposited in the EMBL-EBI ArrayExpress repository (E-MTAB-4591)
2020-07-31 | E-MTAB-9044 | biostudies-arrayexpress
Project description:We describe that Hnf1α and Foxa3 dramatically facilitate the robust generation of iHepSCs. Notably, the prolonged in vitro culture of Hnf1α and Foxa3 derived iHepSCs induce Notch signaling-mediated secondary conversion into cholangiocyte progenitor-like cells displaying the dramatically enhanced differentiation capacity into the mature cholangiocytes in vitro and in vivo. Our study provides the novel two-step approach for obtaining cholangiocyte progenitor-like cells using defined factors.
2018-03-06 | GSE97507 | GEO