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Series GSE263713 Query DataSets for GSE263713
Status Public on Apr 17, 2024
Title Fibroblasts as an in vitro model of circadian genetic and genomic studies: A temporal analysis (RNA-Seq)
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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
 
Overall design To identify broad circadian genetic features on a circadian in vitro fibroblast model, we stablished skin fibroblast primary cell cultures from 6 healthy, control individuals
We then performed gene expression profiling analysis using data obtained from RNA-seq of the 6 different cell lines at 13 time points.
We analyzed temporal changes in gene expression for these fibroblast cells.
Web link https://pubmed.ncbi.nlm.nih.gov/38960898/
 
Contributor(s) Francia M, Bot M, Boltz T, De la Hoz J, Boks M, Kahn R, Ophoff R
Citation(s) 38960898
Submission date Apr 10, 2024
Last update date Jul 28, 2024
Contact name Marcelo Francia
E-mail(s) marcelofrancia@g.ucla.edu
Phone 3104297632
Organization name University of California, Los Angeles
Department Neuroscience
Lab Roel Ophoff
Street address 1771 Beloit Avenue, Unit 204
City Los Angeles
State/province CA
ZIP/Postal code 90025
Country USA
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (78)
GSM8197070 RNA Individual 1 skin fibroblast cells, Dexamethasone, Time0
GSM8197071 RNA Individual 1 skin fibroblast cells, Dexamethasone, Time4
GSM8197072 RNA Individual 1 skin fibroblast cells, Dexamethasone, Time8
This SubSeries is part of SuperSeries:
GSE263714 Fibroblasts as an in vitro model of circadian genetic and genomic studies: A temporal analysis
Relations
BioProject PRJNA1098769

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE263713_raw_counts.tsv.gz 4.7 Mb (ftp)(http) TSV
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