Ontology highlight
ABSTRACT:
PROVIDER: PRJNA597015 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Deregulation of neuro-developmental genes and primary cilium cytoskeleton anomalies in iPSC retinal sheets from human syndromic ciliopathies
| PRJNA550448 | ENA
Project description:Human retinal pigment epithelial (RPE) cells were treated with the sesquiterpene lactones α-cyclocostunolide (α-C) or Grosheimin to investigate their effects on primary cilium structure and associated signaling pathways. Sesquiterpene lactones (SLs) are plant-derived metabolites known for diverse pharmacological activities. Previous studies have shown that certain SLs can alter primary cilium morphology; however, their impact on ciliary signaling remains unclear. This dataset explores the transcriptional changes induced by α-C and Grosheimin in RPE cells. RNA sequencing was performed to identify gene expression changes related to ciliogenesis, microtubule organization, and Hedgehog (Hh) signaling. These data contribute to understanding how structurally distinct SLs modulate ciliary function and may inform future studies on ciliopathies and tumor biology.
2025-11-20 | E-MTAB-15939 | biostudies-arrayexpress
Project description:We used single cell RNA sequencing to investigate the cell diversity in our in vitro differentiation from iPSC to Retinal sheets culture and the development of our culture.
2024-06-30 | GSE228436 | GEO
Project description:Centriolar satellites are an array of membrane-less granules that localize and move around the vertebrate centrosome/cilium complex. They have recently emerged as key regulators of the biogenesis and function of the centrosome/cilium-complex and their mutations are linked to ciliopathies. Although centriolar satellites are ubiquitous structures of the vertebrate cells, their precise function and molecular mechanism of action in different cell types remain poorly understood. Here, we generated kidney and retinal epithelial cells that lack centriolar satellites by genetically ablating their scaffolding protein PCM1 and investigated the cellular and molecular consequences of satellite loss in cells. We showed that centriolar satellites are required for cilium assembly, regulation of ciliary content, timely response to Hedgehog signals and three- dimensional epithelial cell organization, but not for cell proliferation, cell cycle progression and centriole duplication. Importantly, the requirement for centriolar satellites in cilium assembly varied between retinal and kidney epithelial cells and we identified the differences in the efficiency of targeting key ciliogenesis factors to the centrosome including Mib1 and Talpid3 as the likely molecular basis for this phenotypic variability. Quantitative global transcriptomic and proteomic profiling of satellite-less cells showed that loss of centriolar satellites does not lead to a major transcriptional response, but leads to a significant rearrangement of the global proteome. Together, our findings identify important roles for centriolar satellites in key cilium-related cellular processes through regulating the proteostasis and centrosomal/ciliary targeting of proteins and provide insight into the disease mechanisms of ciliopathies.
2018-11-28 | GSE123017 | GEO
Project description:Background Ciliopathies are genetic disorders affecting primary cilia, most commonly affecting the kidney and liver. Although pancreatic cysts have been described in syndromic ciliopathies, the pancreas is not commonly recognized as a target organ. However, several ciliary gene knockout mouse models develop a pancreatic phenotype characterized by acinar atrophy and adipocyte accumulation, hereby called adipopancreatosis, suggesting a link between ciliary dysfunction and pancreatic disease. Objective To investigate whether mutations in ciliopathy-associated genes are associated with pancreatic dysfunction in humans, and to explore the underlying mechanisms. Design We analyzed a cohort of 341 patients with pediatric-onset pancreatic anomalies. In parallel, we generated Nphp3 patient-specific and conditional knockout mouse models to characterize pancreatic alterations at histological, molecular, and cellular levels. In patients, pancreatic fat content was quantified using Dixon-MRI. Results Mutations in HNF1B and NPHP3 were identified in patients presenting both renal ciliopathy and pancreatic dysfunction. Nphp3 mutant and conditional knockout mice developed progressive adipopancreatosis with acinar atrophy and distinct inflammatory profiles. Transcriptomic analyses indicated that the adipocytes displayed a white adipocyte–like gene expression profile and mesothelial-derived fibroblasts were implicated as a likely cellular origin. Additional pathological features included ductal cilium alterations and acinar microcysts. Consistent with the mouse phenotype, Dixon-MRI in patients with HNF1B and NPHP3 mutations demonstrated significantly increased pancreatic fat content. Conclusion We describe a previously unrecognized pancreatic manifestation of ciliopathies, which we term ciliogenic pancreatopathy. Our findings suggest that patients with known ciliopathy-associated mutations should be evaluated for this pancreatic condition during clinical assessments, particularly those with kidney disease, as concomitant exocrine pancreatic insufficiency may further compromise renal function or the outcome of kidney graft.
2026-07-14 | GSE333660 | GEO
Project description:Background Ciliopathies are genetic disorders affecting primary cilia, most commonly affecting the kidney and liver. Although pancreatic cysts have been described in syndromic ciliopathies, the pancreas is not commonly recognized as a target organ. However, several ciliary gene knockout mouse models develop a pancreatic phenotype characterized by acinar atrophy and adipocyte accumulation, hereby called adipopancreatosis, suggesting a link between ciliary dysfunction and pancreatic disease. Objective To investigate whether mutations in ciliopathy-associated genes are associated with pancreatic dysfunction in humans, and to explore the underlying mechanisms. Design We analyzed a cohort of 341 patients with pediatric-onset pancreatic anomalies. In parallel, we generated Nphp3 patient-specific and conditional knockout mouse models to characterize pancreatic alterations at histological, molecular, and cellular levels. In patients, pancreatic fat content was quantified using Dixon-MRI. Results Mutations in HNF1B and NPHP3 were identified in patients presenting both renal ciliopathy and pancreatic dysfunction. Nphp3 mutant and conditional knockout mice developed progressive adipopancreatosis with acinar atrophy and distinct inflammatory profiles. Transcriptomic analyses indicated that the adipocytes displayed a white adipocyte–like gene expression profile and mesothelial-derived fibroblasts were implicated as a likely cellular origin. Additional pathological features included ductal cilium alterations and acinar microcysts. Consistent with the mouse phenotype, Dixon-MRI in patients with HNF1B and NPHP3 mutations demonstrated significantly increased pancreatic fat content. Conclusion We describe a previously unrecognized pancreatic manifestation of ciliopathies, which we term ciliogenic pancreatopathy. Our findings suggest that patients with known ciliopathy-associated mutations should be evaluated for this pancreatic condition during clinical assessments, particularly those with kidney disease, as concomitant exocrine pancreatic insufficiency may further compromise renal function or the outcome of kidney graft.
2026-07-14 | GSE333792 | GEO
Project description:Three-dimensional retinal organoids (3D-retinas) are a promising graft source for transplantation therapy. We previously developed self-organizing culture for 3D-retina generation from human induced pluripotent stem cells (hiPSCs). Toward clinical applications on hPSC-derived retinal sheets, the establishment of a quality control (QC) strategy for 3D-retinas and dissected retinal sheets has remained a major challenge. We performed a microarray analysis for retinal tissue and off-target tissue to identify the major off-target tissue in hiPSC-culture.
2022-02-26 | GSE197446 | GEO
Project description:Transforming Growth Factor-Beta-Activated Kinase 1 (TAK1/MAP3K7), along with its upstream regulators TAK1-Binding Protein 2 (TAB2) and the catalytic alpha-subunit of Protein Kinase A (PKA-Cα/PRKACA), has been identified as a pivotal player in regulation of developmental processes. Haploinsufficiency of TAB2 causes Congenital Heart Disease (CHD) and rare variants in PKA-Cα and TAK1 cause cardioacrofacial dysplasia (CAFD), and Frontometaphyseal Dysplasia (FMD) and cardiospondylocarpofacial syndrome (CSCFS), respectively, rare multisystem syndromes, where CHD may appear in the clinical spectrum. We hypothesized that TAK1 plays a significant role in heart development and CHD and addressed this by genetic analysis in CHD patient cohorts and experiments in cell and animal models. Exome sequencing data from 1,471 CHD patients with extracardiac anomalies (syndromic CHD, sCHD), 2,405 patients with nonsyndromic CHD (nsCHD) and 45,082 controls showed increased burden of rare TAB2 and TAK1 variants in sCHD, but not in nsCHD. Detailed characterization of tak1-/- and tab2-/- zebrafish mutants revealed cardiac defects (dilated atrium, trabeculation defects, tachycardia and reduced contractility) as well as extracardiac developmental anomalies. RNA sequencing of tak1-/- mutant hearts showed downregulation of genes encoding core cardiac transcription factors, sarcomeric proteins and extracellular matrix proteins. Experiments with cell cultures and analysis of zebrafish larvae and gastruloids indicated that TAK1 via TAB2 and PKA-Cα is activated at the primary cilium during cardiomyogenesis and that TAK1 activation at this site is enhanced by cardiomyogenic signaling molecules, including ligands of the TGFB/BMP superfamily. Consistent with these findings, CRISPR/Cas9-mediated editing of TAK1 or administration of small molecule inhibitors targeting TAK1 inhibited ciliary signaling and cardiomyocyte differentiation in vitro, while FMD-causing mutations in TAK1 reduced its ciliary localization. In conclusion, our data establishes a central role for TAK1 and its upstream regulators in cardiac development and syndromic CHD, coordinated via the primary cilium.
2024-10-16 | GSE279246 | GEO
Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.
2015-09-02 | E-MTAB-2894 | biostudies-arrayexpress
Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.
2015-09-02 | E-MTAB-2895 | biostudies-arrayexpress