Dataset Information

Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks.

ABSTRACT: Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneously. We present a temporal and spatial atlas of circadian metabolism in the context of systemic energy balance and under chronic nutrient stress (high-fat diet [HFD]). Comparative analysis reveals how the repertoires of tissue metabolism are linked and gated to specific temporal windows and how this highly specialized communication and coherence among tissue clocks is rewired by nutrient challenge. Overall, we illustrate how dynamic metabolic relationships can be reconstructed across time and space and how integration of circadian metabolomics data from multiple tissues can improve our understanding of health and disease.

SUBMITTER: Dyar KA

PROVIDER: S-EPMC6501776 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks.

Dyar Kenneth A KA Lutter Dominik D Artati Anna A Ceglia Nicholas J NJ Liu Yu Y Armenta Danny D Jastroch Martin M Schneider Sandra S de Mateo Sara S Cervantes Marlene M Abbondante Serena S Tognini Paola P Orozco-Solis Ricardo R Kinouchi Kenichiro K Wang Christina C Swerdloff Ronald R Nadeef Seba S Masri Selma S Magistretti Pierre P Orlando Valerio V Borrelli Emiliana E Uhlenhaut N Henriette NH Baldi Pierre P Adamski Jerzy J Tschöp Matthias H MH Eckel-Mahan Kristin K Sassone-Corsi Paolo P

Cell 20180901 6

Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneously. We present a temporal and spatial atlas of circadian metabolism in the context of systemic energy balance and under chronic nutrient stress (high- ...[more]

PMID: 30193114

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Project description:We report two sets of potential circadian clock target genes by high-throughput transcriptome profiling (RNA-sequencing): one set from the corpus callosum of the adult mouse brain and the other set from adult neural stem cell cultured from the SVZ (neurospheres) of the mouse brain. First, the corpus callosum was dissected from three adult wild-type and two Bmal1 knockout (Bmal1-/-) mice, mRNA profiles were generated by deep sequencing using BGISEQ-500 RNA-Seq platform. The sequence reads that passed quality control were analyzed: we mapped more than 21 million total clean reads, more than 96% total Mapping Ratio, more than 86% Uniquely Mapping Ratio per sample to mouse genome. qRT-PCR validation with primers covering at least 3 known housekeeping genes and at least 5 well-known circadian clock genes were performed with SYBR Green assay. 103 differentially expressed genes (DEGs) were identified in the corpus callosum of Bmal1-/- mice (58 up-regulated and 45 down-regulated genes; |log2FC| > 1 & adjusted P-value < 0.05). Hypergeometric test revealed that potential functions of circadian clock target genes in the corpus callosum are secreted proteins as signaling molecules. For the second set of data, neurospheres were cultured from the SVZ of three adult wild-type and three adult Bmal1-/- mice, mRNA profiles were generated by deep sequencing using BGISEQ-500 RNA-Seq platform. The sequence reads that passed quality control were analyzed: we mapped more than 28 million total clean reads, more than 97% total Mapping Ratio, more than 68% Uniquely Mapping Ratio per sample to mouse genome. qRT-PCR validation with at least 3 known housekeeping genes and at least 5 well-known circadian clock genes using SYBR Green assay. 30 DEGs were identified in neurospheres cultured from Bmal1-/- mice (17 up-regulated and 13 down-regulated genes; |log2FC| > 1 & adjusted P-value < 0.05). Gene Set Enrichment Analysis (GSEA) revealed that potential circadian clock associated functions in the SVZ (neurospheres) are controlling diverse signal transductions.

Dataset Information

Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks.

Publications

Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks.

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