Your browser doesn't support javascript.
loading
Fibroblasts as an in vitro model of circadian genetic and genomic studies.
Francia, Marcelo; Bot, Merel; Boltz, Toni; De la Hoz, Juan F; Boks, Marco; Kahn, René S; Ophoff, Roel A.
Afiliação
  • Francia M; Interdepartmental Program for Neuroscience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. marcelofrancia@g.ucla.edu.
  • Bot M; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
  • Boltz T; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • De la Hoz JF; Bioinformatics Interdepartamental Program, University of California Los Angeles, Los Angeles, CA, USA.
  • Boks M; Department Psychiatry, Brain Center University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.
  • Kahn RS; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Ophoff RA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
Mamm Genome ; 35(3): 432-444, 2024 Sep.
Article em En | MEDLINE | ID: mdl-38960898
ABSTRACT
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 h 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 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Bipolar / Ritmo Circadiano / Fibroblastos Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Bipolar / Ritmo Circadiano / Fibroblastos Idioma: En Ano de publicação: 2024 Tipo de documento: Article