Fibroblasts as an in vitro model of circadian genetic and genomic studies: A temporal analysis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1098765 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28620400_1.fastq.gz | Fastqsanger.gz | |||
| SRR28620400_2.fastq.gz | Fastqsanger.gz | |||
| SRR28620401_1.fastq.gz | Fastqsanger.gz | |||
| SRR28620401_2.fastq.gz | Fastqsanger.gz | |||
| SRR28620402_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 230 |
Similar Datasets
Project description:Bipolar disorder (BD) is a heritable disorder characterized by shifts in mood that manifest in manic or depressive episodes. Clinical studies have identified abnormalities of the circadian system in BD patients as a hallmark of underlying pathophysiology. Fibroblasts are a well-established in vitro model for measuring circadian patterns. We set out to examine the underlying genetic architecture of circadian rhythm in fibroblasts, with the goal to assess its contribution to the polygenic nature of BD disease risk. We collected, from primary cell lines of 6 healthy individuals, temporal genomic features over a 48 hour period from transcriptomic data (RNA-seq) and open chromatin data (ATAC-seq). The RNA-seq data showed that only a limited number of genes, primarily the known core clock genes such as ARNTL, CRY1, PER3, NR1D2 and TEF display circadian patterns of expression consistently across cell cultures. The ATAC-seq data identified that distinct transcription factor families, like those with the basic helix-loop-helix motif, were associated with regions that were increasing in accessibility over time. Whereas known glucocorticoid receptor target motifs were identified in those regions that were decreasing in accessibility. Further evaluation of these regions using stratified linkage disequilibrium score regression (sLDSC) analysis failed to identify a significant presence of them in the known genetic architecture of BD, and other psychiatric disorders or neurobehavioral traits in which the circadian rhythm is affected. In this study, we characterize the biological pathways that are activated in this in vitro circadian model, evaluating the relevance of these processes in the context of the genetic architecture of BD and other disorders, highlighting its limitations and future applications for circadian genomic studies
2024-04-17 | GSE263713 | GEO
Project description:Bipolar disorder (BD) is a heritable disorder characterized by shifts in mood that manifest in manic or depressive episodes. Clinical studies have identified abnormalities of the circadian system in BD patients as a hallmark of underlying pathophysiology. Fibroblasts are a well-established in vitro model for measuring circadian patterns. We set out to examine the underlying genetic architecture of circadian rhythm in fibroblasts, with the goal to assess its contribution to the polygenic nature of BD disease risk. We collected, from primary cell lines of 6 healthy individuals, temporal genomic features over a 48 hour period from transcriptomic data (RNA-seq) and open chromatin data (ATAC-seq). The RNA-seq data showed that only a limited number of genes, primarily the known core clock genes such as ARNTL, CRY1, PER3, NR1D2 and TEF display circadian patterns of expression consistently across cell cultures. The ATAC-seq data identified that distinct transcription factor families, like those with the basic helix-loop-helix motif, were associated with regions that were increasing in accessibility over time. Whereas known glucocorticoid receptor target motifs were identified in those regions that were decreasing in accessibility. Further evaluation of these regions using stratified linkage disequilibrium score regression (sLDSC) analysis failed to identify a significant presence of them in the known genetic architecture of BD, and other psychiatric disorders or neurobehavioral traits in which the circadian rhythm is affected. In this study, we characterize the biological pathways that are activated in this in vitro circadian model, evaluating the relevance of these processes in the context of the genetic architecture of BD and other disorders, highlighting its limitations and future applications for circadian genomic studies
2024-04-17 | GSE263711 | GEO
Project description:Fibroblasts as an in vitro model of circadian genetic and genomic studies: A temporal analysis (RNA-Seq)
| PRJNA1098769 | ENA
Project description:Fibroblasts as an in vitro model of circadian genetic and genomic studies: A temporal analysis (ATAC-Seq)
| PRJNA1098762 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-17 | GSE263714 | GEO
Project description:In vitro methylation studies in human fibroblasts from progeria cases
| PRJNA823349 | ENA
Project description:High-temporal resolution profiling was performed on U2OS fibroblasts to detect rhythmic transcripts Keywords: time course
2008-12-15 | GSE13949 | GEO
Project description:Membrane type I-matrix metalloproteinase (MT1-MMP/Mmp14) is an unusual MMP because it is essential for survival in mice with multiple organ systems being affected for reasons that are unclear. Here, we show that the protein (MT1-MMP) and gene (Mmp14) are under strict circadian clock control and conditional knockout in fibroblasts leads to ~16% of the proteome losing or inverting circadian rhythmicity. The result is loss of the actin cytoskeleton and cell-matrix adhesions and major imbalance of the matrisome. Lack of collagen-I monomer turnover results in excess fibril formation in the absence of Mmp14. In the absence of Mmp14, paired-like homeodomain transcription factor 2 (Pitx2) is upregulated and remains in the nucleus where it drives Plod2 expression. The overall result is accumulation of collagen fibrils and elevated pyridinoline crosslinking that renders collagen fibrils insoluble. In conclusion, Mmp14 is a master regulator of circadian rhythms affecting the actin cytoskeleton and cell microenvironment.
2023-10-31 | PXD031692 | Pride
Project description:The circadian system plays an essential role in regulating timing of body metabolism in humans. Indeed, circadian misalignments are strongly associated with high rates of metabolic disorders. Molecular makeup of the circadian oscillator can be deciphered in cells cultured in vitro, and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo.
We aimed at assessing molecular clock properties in dermal fibroblasts established from the skin biopsies of seventeen Type 2 diabetic obese and non-obese patients and eleven healthy controls. Following in vitro synchronization, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters.
We observed a strong inverse correlation between HbA1c values and circadian period length within cells from the Type 2 diabetic group. RNA sequencing analysis conducted in this group samples revealed that ICAM1 encoding for the endothelial adhesion protein was differentially expressed between Type 2 diabetic compensated and non-compensated fibroblasts, and correlated with the period length. Furthermore, ICAM1 expression is driven by rhythmic CLOCK binding.
We provide for the first time a potential molecular link between severity of Type 2 diabetes and circadian clock machinery, which paves a way for further mechanistic understanding of circadian oscillator changes upon Type 2 diabetes in humans.
| EGAS00001003622 | EGA
Project description:To screen for specific circadian outputs that may distinguish the pacemaker in the mammalian suprachiasmatic nucleus (SCN) from peripheral-type oscillators in which the canonical clockworks are similarly regulated in a circadian manner, the rhythmic behavior of the transcriptome in forskolin-stimulated NIH/3T3 fibroblasts was analyzed and compared to that found in the rat SCN in vivo and SCN2.2 cells in vitro. Similar to the scope of circadian gene expression in SCN2.2 cells and the rat SCN, NIH/3T3 fibroblasts exhibited circadian fluctuations in the expression of the core clock genes, Per2, Bmal1 (Mop3), and Cry1 and 323 functionally diverse transcripts (2.6%), many of which were involved in cell communication. Overlap in rhythmically-expressed transcripts among NIH/3T3 fibroblasts, SCN2.2 cells and the rat SCN was limited to these clock genes and four other genes that mediate fatty acid and lipid metabolism or function as nuclear factors. Compared to NIH/3T3 cells, circadian gene expression in SCN oscillators was more prevalent among cellular pathways mediating glucose metabolism and neurotransmission. Coupled with evidence for the rhythmic regulation of the inducible isoform of nitric oxide synthase, the enzyme responsible for the production of nitric oxide, in SCN2.2 cells and the rat SCN but not in fibroblasts, studies examining the effects of a NOS inhibitor on metabolic rhythms in co-cultures containing SCN2.2 cells and untreated NIH/3T3 cells suggest that this gaseous neurotransmitter may play a key role in SCN pacemaker function. Thus, this comparative analysis of circadian gene expression in SCN and non-SCN cells may have important implications in the selective identification of circadian signals involved in the coupling of SCN oscillators and the regulation of rhythmicity in downstream cells or tissues. Keywords: Circadian time course
2006-10-31 | GSE5810 | GEO