Effect of loss of ciliogenesis on myoblast quiescence
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ABSTRACT:
PROVIDER: PRJNA434444 | ENA |
REPOSITORIES: ENA
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Project description:Quiescence is an actively maintained state of the cell cycle;aberrations in which can result in severe consequencces for development and tissue homeostasis. Primary cilia are signaling centres derived from the centrosome which are associated with quiescence.Using a mouse skeletal myoblast cell culture system that can be induced to exit the cell cycle reversibly into quiescence or irreversibly into differentiation, we studied the effect of loss of ciliogenesis on quiescence.
2018-12-31 | GSE110742 | GEO
Project description:Microtubule actin crosslinking factor 1 (Macf1) plays a role in coordinated actions of actin and microtubules in multiple cellular processes. Here we show that Macf1 is also critical for ciliogenesis in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of Macf1 in adult photoreceptors caused reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for Macf1 function. Macf1 was also shown to interact with ciliary proteins Mkks and Talpid3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking Macf1, and that Mkks and Talpid3 are involved in the coordination of microtubule and actin interactions.
2016-11-01 | GSE86997 | GEO
Project description:The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar pancreas tissue homeostasis are poorly understood. Here, we evaluate the role of Par3 in acinar pancreas injury and homeostasis. While Par3 loss in the mouse pancreas disrupts tight junctions, Par3 loss is dispensable for pancreatogenesis. However, with aging, Par3 loss results in low-grade inflammation, acinar degeneration, and pancreatic lipomatosis. Par3 loss also exacerbates pancreatitis-induced acinar cell loss, resulting in pronounced pancreatic lipomatosis and failure to regenerate. Moreover, Par3 loss in mice harboring mutant Kras causes extensive pancreatic intraepithelial neoplastic (PanIN) lesions and large pancreatic cysts. We also show that Par3 loss restricts injury-induced primary ciliogenesis. Significantly, targeting BET proteins enhances primary ciliogenesis during pancreatitis-induced injury and, in mice with Par3 loss, limits pancreatitis-induced acinar loss and facilitates acinar cell regeneration. Combined, this study demonstrates how Par3 restrains pancreatitis- and Kras-induced changes in the pancreas and identifies a potential role for BET inhibitors to attenuate pancreas injury and facilitate pancreas tissue regeneration.
2024-08-05 | GSE243623 | GEO
Project description:Satellite cells (SCs) are adult muscle stem cells residing in a specialised niche that regulates SC homeostasis. How niche-generated signals integrate to regulate gene expression in SC-derived myoblasts, is poorly understood. We undertook an unbiased approach to study the effect of the SC niche on SC-derived myoblast transcriptional regulation and identified the tumour suppressor p53 as a key player in the regulation of myoblast quiescence. After activation and proliferation, a subpopulation of myoblasts cultured in the presence of the niche upregulates p53 and fails to differentiate. When SC self-renewal is modelled ex vivo in a reserve cell assay, myoblasts treated with Nutlin-3, which increases p53 levels in the cell, fail to differentiate and instead become quiescent. Since both these effects of Nutlin-3 are rescued by siRNA-mediated p53 knockdown we conclude that a tight control of p53 levels in myoblasts regulate the balance between differentiation and return to quiescence.
2018-01-11 | GSE109052 | GEO
Project description:Expression profiling of C2C12 myoblast cells treated with ethanol during differentiation. Ethanol inhibits C2C12 differentiation. Results provide insight into signaling pathways altered by ethanol during differentiation.
2013-04-30 | GSE46492 | GEO
Project description:Dysfunction of cell cycle control and defects of primary ciliogenesis are two features of many cancers. Whether these events are interconnected and the driving mechanism controlling and coordinating these events remains largely unknown. Here we identified an actin branching surveillance system that alerts cells for the insufficiency of the actin branching network controlling the restriction point, cytokinesis， and primary ciliogenesis. We found that the ciliopathy protein Oral-Facial-Digital syndrome 1 (OFD1) functions as a previously undescribed class II NPF to promote Arp2/3 complex-mediated actin branching synergistically with class I NPF via its C-terminal acidic domain. Perturbation of actin branching promotes OFD1 degradation and inactivation via a liquid-to-gel transition at centriolar satellites. Elimination of OFD1 or disruption of OFD1-Arp2/3 interaction promotes ciliogenesis and drives proliferating, non-transformed cells into quiescence by an RB-dependent mechanism that is independent of ciliogenesis, senescence, or centrosome loss, which could be reversed by oncogene overactivation. Oncogene-transformed cells, as well as most cancer cells, bypass the G1/S checkpoint in the absence of OFD1 but fail to assemble actin filaments on the actomyosin ring, resulting in incomplete cytokinesis and irreversible mitotic catastrophe. Inhibition of OFD1 leads to marked suppression of pancreatic, colon, and triple-negative breast cancer cell growth in mouse xenograft models. Thus, cancer cells display a major difference from normal cells in their response to the OFD1-mediated actin branching surveillance system, and targeting this surveillance system provides a new direction for cancer therapy.
2023-02-15 | GSE225003 | GEO
Project description:Purpose: To understand the relationship between ciliogenesis and autophagy in the corneal epithelium. Methods: siRNAs for EphA2 or PLD1 were used to inhibit protein expression in vitro. Morpholino-anti-EphA2 was used to knockdown EphA2 in Xenopus skin. An EphA2 knockout mouse was used to conduct loss of function studies. Autophagic vacuoles were visualized by contrast light microscopy. Autophagy flux, was measured by LC3 turnover and p62 protein levels. Immunostaining and confocal microscopy were conducted to visualize cilia in cultured cells and in vivo. Results: Loss of EphA2 (i) increased corneal epithelial thickness by elevating proliferative potential in wing cells, (ii) reduced the number of ciliated cells, (iii) increased large hollow vacuoles, that could be rescued by BafA1; (iv) inhibited autophagy flux and (v) increased GFP-LC3 puncta in the mouse corneal epithelium. This indicated a role for EphA2 in stratified epithelial assembly via regulation of proliferation as well as a positive role in both ciliogenesis and end-stage autophagy. Inhibition of PLD1, an EphA2 interacting protein that is a critical regulator of end-stage autophagy, reversed the accumulation of vacuoles, and the reduction in the number of ciliated cells due to EphA2 depletion, suggesting EphA2 regulation of both end-stage autophagy and ciliogenesis via PLD1. PLD1 mediated rescue of ciliogenesis by EphA2 depletion was blocked by BafA1, placing autophagy between EphA2 signaling and regulation of ciliogenesis. Conclusion: Our findings demonstrate a novel role for EphA2 in regulating both autophagy and ciliogenesis, processes that are essential for proper corneal epithelial homeostasis. Purpose: To understand the relationship between ciliogenesis and autophagy in the corneal epithelium. Methods: siRNAs for EphA2 or PLD1 were used to inhibit protein expression in vitro. Morpholino-anti-EphA2 was used to knockdown EphA2 in Xenopus skin. An EphA2 knockout mouse was used to conduct loss of function studies. Autophagic vacuoles were visualized by contrast light microscopy. Autophagy flux, was measured by LC3 turnover and p62 protein levels. Immunostaining and confocal microscopy were conducted to visualize cilia in cultured cells and in vivo. Results: Loss of EphA2 (i) increased corneal epithelial thickness by elevating proliferative potential in wing cells, (ii) reduced the number of ciliated cells, (iii) increased large hollow vacuoles, that could be rescued by BafA1; (iv) inhibited autophagy flux and (v) increased GFP-LC3 puncta in the mouse corneal epithelium. This indicated a role for EphA2 in stratified epithelial assembly via regulation of proliferation as well as a positive role in both ciliogenesis and end-stage autophagy. Inhibition of PLD1, an EphA2 interacting protein that is a critical regulator of end-stage autophagy, reversed the accumulation of vacuoles, and the reduction in the number of ciliated cells due to EphA2 depletion, suggesting EphA2 regulation of both end-stage autophagy and ciliogenesis via PLD1. PLD1 mediated rescue of ciliogenesis by EphA2 depletion was blocked by BafA1, placing autophagy between EphA2 signaling and regulation of ciliogenesis. Conclusion: Our findings demonstrate a novel role for EphA2 in regulating both autophagy and ciliogenesis, processes that are essential for proper corneal epithelial homeostasis.
2021-05-19 | GSE174649 | GEO
Project description:Effect of depletion of PRR33 on gene expression during myoblast differentiation
| PRJNA1057182 | ENA
Project description:Expression profiling of C2C12 myoblast cells treated with ethanol during differentiation. Ethanol inhibits C2C12 differentiation. Results provide insight into signaling pathways altered by ethanol during differentiation. When C2C12 cells reached 70% confluence in growth medium containing 20% FBS, culture medium was changed to differentiation medium containing 2% horse serum with and without 100mM ethanol. Samples were harvested from day zero (just prior to differentiation) as well as days 1, 2 and 3 following onset of differentiation with and without alcohol treatment. RNA was isolated using the Qiagen RNA mini-kit.
2013-04-30 | E-GEOD-46492 | biostudies-arrayexpress
Project description:To investigate the effects on human muscle precursor cells of a loss of function of Mendelian genes related to familial ALS, such as TARDBP (TDP-43) or FUS, we established human inmortalised myoblast cell lines in which each target gene has been transiently knocked down (KD) by shRNA.
2024-09-25 | GSE227573 | GEO