Similar Datasets
Project description:Skeletal muscle stem cell ciliary pathways
| PRJNA606745 | ENA
Project description:Injured skeletal muscle regenerates, but with age or in muscular dystrophies, muscle is replaced by fat. Upon injury, muscle-resident fibro/adipogenic progenitors (FAPs) proliferated and gave rise to adipocytes. These FAPs dynamically produced primary cilia, structures that transduce intercellular cues such as Hedgehog (Hh) signals. Genetically removing cilia from FAPs inhibited intramuscular adipogenesis, both after injury and in a mouse model of Duchenne muscular dystrophy. Blocking FAP ciliation also enhanced myofiber regeneration after injury and reduced myofiber size decline in the muscular dystrophy model. Hh signaling through FAP cilia regulated the expression of TIMP3, a secreted metalloproteinase inhibitor, that inhibited MMP14 to block adipogenesis. A pharmacological mimetic of TIMP3 blocked the conversion of FAPs into adipocytes, pointing to a strategy to combat fatty degeneration of skeletal muscle. We conclude that ciliary Hh signaling by FAPs orchestrates the regenerative response to skeletal muscle injury.
2017-07-13 | GSE86073 | GEO
Project description:We performed whole genome gene expression profiling in bronchial biopsies from PCD patients. We used the Quality Threshold clustering algorithm to identify groups of genes that revealed highly correlated RNA expression patterns in the biopsies. The largest cluster contained 372 genes and was significantly enriched for genes related to cilia. The database and literature search showed that 16250 genes in this cluster were known cilia genes, strongly indicating that the remaining 21022 genes were likely to be new cilia genes. The tissue expression pattern of the 210 new cilia genes and the 162 known genes was consistent with the presence of motile cilia in a given tissue. Analysis of the upstream promotor sequences revealed evidence for RFX transcription factors binding site motif in both subgroups. Total RNA obtained from 6 primary ciliary dyskinesia patients and 9 control individuals
2015-02-24 | E-GEOD-25186 | biostudies-arrayexpress
Project description:Satellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved in acquisition of muscle stem cell characteristics.
2016-06-15 | GSE63860 | GEO
Project description:Primary cilia are microtubule based sensory organelles that protrude from almost every cell type. Their membrane contains highly specialized receptors important for receiving and processing extracellular signals, which enables them to regulate several signalling pathways. A recently discovered characteristic is that cilia are also able to release extracellular vesicles (EVs) from the ciliary membrane. Since EVs have been shown to exert numerous functions in physiology and pathology, these findings have the potential to dramatically alter our understanding of how the primary cilium is able to regulate various signalling pathways in development and disease. In our study we focused on the release of EVs from a ciliated kidney cell line. Using control and mutant cell lines, in which ciliary trafficking was disrupted, we observed that loss of primary cilia function leads to altered EV secretion and composition in NTA (Nanoparticle Tracking Analysis) and Western blot. Cilia mutant cells released more small EVs compared to control, and their composition was also changed between mutant and control. Protein identification via mass spectrometry identified both cilia- as well as WNT signalling-associated proteins and miRNA sequencing determined WNT-related miRNAs, which were differentially expressed in small EVs isolated from the cilia mutant cell line. Because of the presence of differentially expressed WNT related molecules in these small EVs, we tested whether this would have an effect on the WNT activity of recipient cells. We observed that small EVs secreted from cilia mutant cells differentially modulated the WNT response in recipient cells compared to control. Our results highlight a possible new small EV-dependent ciliary signalling mechanism, since deficient primary cilia lead to a change in EV secretion, resulting in an altered signal transduction. These results provide us with new insights into ciliopathy disease pathogenesis.
2021-07-19 | GSE153227 | GEO
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:ARL13B is a small regulatory GTPase that controls ciliary membrane composition in both motile cilia and non-motile primary cilia. In this study, we investigated the role of ARL13B in the efferent ductules, tubules of the male reproductive tract essential to male fertility in which primary and motile cilia co-exist. We used a genetically engineered mouse model to deleteArl13bin efferent ductule epithelial cells, resulting in compromised primary and motile cilia architecture and functions. This deletion led to disturbances in reabsorptive/secretory processes and triggered an inflammatory response. The observed male reproductive phenotype showed significant variability linked to partial infertility, highlighting the importance of ARL13B in maintaining a proper physiological balance in these small ducts. These results emphasize the dual role of both motile and primary cilia functions in regulating efferent duct homeostasis, offering deeper insights into how cilia related diseases affect the male reproductive system.
2024-09-30 | GSE256400 | GEO
Project description:Direct lineage reprogramming provides a unique system to study cell fate transitions and unearth molecular mechanisms that safeguard cellular identity. We previously reported on direct conversion of mouse fibroblasts into induced myogenic progenitor cells (iMPCs) by transient MyoD overexpression in concert with small molecules treatment. Here we employed integrative multi-omic approaches to delineate the molecular landscape of fibroblast reprogramming into iMPCs in comparison to transdifferentiation into myogenic cells solely by MyoD overexpression. Utilizing bulk RNA-sequencing and mass spectrometry, we uncovered molecular regulators and pathways that endow a myogenic stem cell identity on fibroblasts only in the presence of small molecule treatment. In addition, we demonstrate that Pax7+ cells in iMPCs share molecular attributes with myoblasts, however in addition express unique genes, proteins and pathways that are indicative of a more activated satellite cell-like state in vitro. Collectively, this study charts a molecular blueprint for reprogramming fibroblasts into muscle stem and progenitor cells and further establishes the fidelity of stable iMPC cultures in capturing skeletal muscle regeneration in vitro for disease modeling and basic research applications.
2022-05-19 | PXD029379 | Pride
Project description:Satellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved in acquisition of muscle stem cell characteristics. Muscle samples were isolated from the trunk during development, postnatally and in adult and aged Pax3GFP/+ mice. After digestion, GFP cells were purified via FACS and process for RNA extraction and hybridization on Affymetrix microarrays (Affymetrix Mouse Genome 430 2.0 Arrays). The different ages selected for sample isolation were E11.5-E12.5-E13.5-E14.5-E15.5-E17.5-P1-P12-1MO-2MO-18MO (E, Embryonic days; P, Postnatal days; MO, age in months), covering embryonic and fetal progenitors and proliferant, quiescent satellite cells. The eleven stages were done in triplicate for E11.5-E12.5-E14.5-E15.5-1MO-2MO-18MO, twice for E13.5, 4 times for P1-P12 and 5 times for E17.5, so 36 samples included in the microarray.
2016-06-15 | E-GEOD-63860 | biostudies-arrayexpress
Project description:Satellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved during early postnatal growth till acquisition of satellite cell quiescence.
2015-04-21 | GSE65927 | GEO