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Status |
Public on Jan 01, 2018 |
Title |
Ionizing radiations potentiate high fat diet-induced insulin resistance and reprogram skeletal muscle and adipose progenitor cells |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Methylation profiling by high throughput sequencing
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Summary |
Exposure to ionizing radiation increases the risk of chronic metabolic disorders such as insulin resistance and type 2 diabetes later in life. We hypothesized that irradiation reprograms the epigenome of metabolic progenitor cells, which could account for impaired metabolism after cancer treatment. C57Bl/6 mice were treated with a single dose of irradiation and subjected to high fat diet (HFD). RNA Sequencing and Reduced Representation Bisulfite Sequencing were used to create transcriptomic and epigenomic profiles of preadipocytes and skeletal muscle satellite cells collected from irradiated mice. Mice subjected to total body irradiation showed alterations in glucose metabolism and, when challenged with HFD, marked hyperinsulinemia. Insulin signaling was chronically disrupted in skeletal muscle and adipose progenitor cells collected from irradiated mice and differentiated in culture. Epigenomic profiling of skeletal muscle and adipose progenitor cells from irradiated animals revealed substantial DNA methylation changes, notably for genes regulating the cell cycle, glucose/lipid metabolism and expression of epigenetic modifiers. Our results show that total body irradiation alters intracellular signaling and epigenetic pathways regulating cell proliferation and differentiation of skeletal muscle and adipose progenitor cells, and provide a possible mechanism by which irradiation used in cancer treatment increases the risk for metabolic disease later in life.
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Overall design |
Reduced representation bisulfite sequencing (RRBS), RNA-Seq and Methyl-CpG-binding domain sequencing (MBD-Seq) of SVF and satellite cells, on CHOW or HFD and untreated or irradiatedÂ
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Contributor(s) |
Nylander VC, Ingerslev LR, Andersen E, Fabre OM, Garde C, Rasmussen M, Citirikkaya K, Baek J, Christensen GL, Aznar M, Specht L, Simar D, Barres R |
Citation(s) |
27650856 |
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Submission date |
Aug 31, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Lars Roed Ingerslev |
E-mail(s) |
ingerslev@sund.ku.dk
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Organization name |
Copenhagen University
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Department |
NNF Center for Basic Metabolic Research
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Lab |
Integrative Physiology
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Street address |
Blegdamsvej 3B
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City |
Copenhagen |
ZIP/Postal code |
2200 |
Country |
Denmark |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (96)
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Relations |
BioProject |
PRJNA341351 |
SRA |
SRP083872 |
Supplementary file |
Size |
Download |
File type/resource |
GSE86280_MBD.xlsx.gz |
515.4 Kb |
(ftp)(http) |
XLSX |
GSE86280_RNA.xlsx.gz |
359.4 Kb |
(ftp)(http) |
XLSX |
GSE86280_RRBS_SVF.xlsx.gz |
2.7 Mb |
(ftp)(http) |
XLSX |
GSE86280_RRBS_satelliteCells.xlsx.gz |
3.6 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Processed data are available on Series record |
Raw data are available in SRA |
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