Il-17 p53 Developmental Series
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE229132 | GEO | 2024/01/30
REPOSITORIES: GEO
Similar Datasets
Project description:Metazoan growth and development requires the coordination of cell cycle progression and metabolism with nutrient availability1-3. Here, we show that in C. elegans, amphid neurons regulate the animals’ developmental decision to continue reproductive growth or arrest as quiescent dauer larvae in response to food, by controlling the activity of C. elegans p53-like ortholog, CEP-1. Specifically, upon food availability, larval neurons secrete a mammalian IL-17 ortholog, ILC-17.1, and ILC-17.1 signaling is needed for C. elegans to progress through development into reproductive adults. ILC-17.1 deficiency activates CEP-1/p53 in larval blast cells, and causes larvae to arrest as stress-resistant, quiescent dauers by activating DAF-16/FOXO, decreasing cytochrome C levels, decreasing glucose utilization and upregulating cell cycle inhibitors. Increasing ILC-17.1 levels represses CEP-1/p53 and promotes anabolic growth, but also inhibits apoptosis upon genotoxic stress. IL-17 also represses p53 in human epithelial cells. These studies describe a role for the tumor suppressor p53-like proteins in controlling developmental quiescence of a metazoan in response to neuronal activity and immunometabolic signals and are relevant to our understanding of neuroimmune mechanisms in cancer. This novel role for p53-like proteins in C. elegans supports the argument that their developmental function was a main driving force in their evolution4,5.
2024-01-30 | GSE218596 | GEO
Project description:The whole-animal transcriptomes of ilc-17.1, malt-1 and nfki-1 mutants comapared to that of controls reveals a transcriptional fingerprint of C. elegans IL-17 signaling.
2020-03-25 | GSE144057 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE30977: C. elegans: Dauers and Dauer-Exit at 12 hour time-point vs. Mix-stage worms GSE31861: P. pacificus : Dauers and Dauer-Exit at 12 hour time-point vs. Mix-stage worms Refer to individual Series
2012-03-22 | E-GEOD-36644 | biostudies-arrayexpress
Project description:Very little is known about the genetic modulation of nictation, a host-finding strategy used by infective juveniles of many pathogenic nematodes, as well as a phoretic strategy of Caenorhabditis elegans dauers. We here use a mass spectrometry-driven approach to find neuropeptides involved in the modulation of this behavior. We identified 126 neuropeptides in infective juveniles of the commercially relevant entomopathogenic nematode Steinernema carpocapsae, 75 of which have orthologs in the model organism C. elegans. To prioritize candidates for causality testing in light of the stage-restricted nictation behavior, we developed quantitative peptidomic assays and carried out targeted proteomic measurements that allows comparing neuropeptide levels at different C. elegans life stages. Our results show that virtually all 164 quantified neuropeptides are more abundant in dauers compared to L3 juveniles. Even so, not all are relevant to nictation, and we identify the neuropeptide genes flp-7 and flp-11 as novel regulators of nictation.
2022-12-08 | PXD034629 | Pride
Project description:Early environmental experiences and life histories profoundly influence adult phenotypes via as yet poorly understood mechanisms. We previously showed that wild-type adult C. elegans that transiently passed through the stress-induced dauer larval stage (post-dauers) exhibit different gene expression patterns, genome-wide chromatin structure, and life history traits when compared to adults that bypassed the dauer stage (controls). Here we show that endogenous small inhibitory RNAs (endo-siRNAs) and siRNA pathways may mediate developmental history-dependent phenotypic diversity. Deep sequencing of small RNA libraries show changes in endo-siRNA levels in post-dauer as compared to control animals, and meta analyses indicate that specific endo-siRNA pathways are targets of developmental history-dependent reprogramming. We demonstrate that mutations in specific endo-siRNA pathways affect the expected gene expression and chromatin state changes in post-dauer animals, and also disrupt their increased brood size phenotype. We find that the chromatin state and endo-siRNA distribution in dauers is also distinct and suggest that this remodeling in dauers provides a template for the subsequent establishment of adult post-dauer profiles. Together, our results imply a critical mechanistic role for endo-siRNA pathways in mediating early experience-dependent phenotypic divergence in adults, and suggest that regulation of these pathways contribute to increased fitness via non-genetic mechanisms.
2013-04-05 | GSE33313 | GEO
Project description:Background: Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA-Sequencing of non-degenerated and degenerated CEP cells were performed. Methods: Human lumbar CEP cells from degenerated (Thompson Grade ≥ 4) and non-degenerated (Thompson Grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated, N=4 degenerated) and single-cell (N=1 non-degenerated, N=1 degenerated) RNA-Sequencing. Genes identified from bulk RNA-Sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared. A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues. For single-cell RNA-Sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation. Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples. Results: Bulk RNA-Sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|Fold change| ≥ 1.5). Of these, only 2 genes were previously studied in CEP cells and 31 were previously studied in the IVD and other cartilaginous tissues. Single-cell RNA-Sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles. Analysis of genes in the bulk RNA-Sequencing dataset showed that progenitor cell clusters from both samples were enriched in “non-degenerated” genes, but not “degenerated” genes. For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction. Conclusions: This thorough analysis using RNA-Sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration.
2024-01-10 | GSE242443 | GEO
Project description:Background: Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA-Sequencing of non-degenerated and degenerated CEP cells were performed. Methods: Human lumbar CEP cells from degenerated (Thompson Grade ≥ 4) and non-degenerated (Thompson Grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated, N=4 degenerated) and single-cell (N=1 non-degenerated, N=1 degenerated) RNA-Sequencing. Genes identified from bulk RNA-Sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared. A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues. For single-cell RNA-Sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation. Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples. Results: Bulk RNA-Sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|Fold change| ≥ 1.5). Of these, only 2 genes were previously studied in CEP cells and 31 were previously studied in the IVD and other cartilaginous tissues. Single-cell RNA-Sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles. Analysis of genes in the bulk RNA-Sequencing dataset showed that progenitor cell clusters from both samples were enriched in “non-degenerated” genes, but not “degenerated” genes. For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction. Conclusions: This thorough analysis using RNA-Sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration.
2024-01-10 | GSE242040 | GEO
Project description:Early environmental experiences and life histories profoundly influence adult phenotypes via as yet poorly understood mechanisms. We previously showed that wild-type adult C. elegans that transiently passed through the stress-induced dauer larval stage (post-dauers) exhibit different gene expression patterns, genome-wide chromatin structure, and life history traits when compared to adults that bypassed the dauer stage (controls). Here we show that endogenous small inhibitory RNAs (endo-siRNAs) and siRNA pathways may mediate developmental history-dependent phenotypic diversity. Deep sequencing of small RNA libraries show changes in endo-siRNA levels in post-dauer as compared to control animals, and meta analyses indicate that specific endo-siRNA pathways are targets of developmental history-dependent reprogramming. We demonstrate that mutations in specific endo-siRNA pathways affect the expected gene expression and chromatin state changes in post-dauer animals, and also disrupt their increased brood size phenotype. We find that the chromatin state and endo-siRNA distribution in dauers is also distinct and suggest that this remodeling in dauers provides a template for the subsequent establishment of adult post-dauer profiles. Together, our results imply a critical mechanistic role for endo-siRNA pathways in mediating early experience-dependent phenotypic divergence in adults, and suggest that regulation of these pathways contribute to increased fitness via non-genetic mechanisms. We deep-sequenced small RNA libraries from 2 biological replicates each of control and postdauer adults, and one biological each of larval L3 and dauer stages.
2013-04-05 | E-GEOD-33313 | biostudies-arrayexpress
Project description:CEP-37440 at low concentration (1,000 nM) decreased the proliferation of the human inflammatory breast cancer (IBC) cell line FC-IBC02, while not affecting the proliferation of normal breast epithelial cells. CEP-37440 decreased the cell proliferation of FC-IBC02 by blocking the auto-phosphorylation kinase activity of FAK (Tyr 397). This cell line did not expressed ALK. In vivo, CEP-37440 significantly decreased FC-IBC02 breast tumor xenografts growth with maximum of 40% tumor growth inhibition. None of the FC-IBC02 breast xenografts mice treated with CEP-37440 developed brain metastasis in contrast to the control group in which 20% of the mice developed brain metastasis. Expression array analyses in FC-IBC02 cells showed that CEP-37440 affects the expression of genes related to apoptosis specifically related to the interferon signaling pathway. Cell proliferation assays were performed in the presence of several concentrations of CEP-37440 using IBC and triple negative breast cancer (TNBC) non-IBC cell lines. We studied the expression of total FAK1, phospho-FAK1 (Tyr 397), total ALK and phospho-ALK (Tyr 1604) in these cells by ELISA. FC-IBC02 cells were treated with 1,000 nM CEP-37440 during 48 h, and expression arrays were performed in order to define pathways dysregulated by CEP-37440.
2015-12-14 | E-GEOD-73285 | biostudies-arrayexpress