NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE109671 Query DataSets for GSE109671
Status Public on Jun 27, 2018
Title Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Other
Genome binding/occupancy profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
Summary Background: Ageing is characterised by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of ageing on B cell development, we have profiled gene expression and chromatin features, including histone modifications and chromosome conformation focused on promoter interactions, globally in murine bone marrow pro-B and pre-B cells.

Results: Our analysis revealed that the expression levels of most genes are generally preserved in B cell precursors isolated from aged as compared to young mice. Nonetheless, age-specific expression changes are observed at numerous genes and are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions and nuclear compartmentalisation. We identified transcriptional downregulation of components of the insulin-like growth factor signalling pathway, in particular downregulation of Irs1 and upregulation of miR/Let-7 expression, as a signature of the aged phenotype. Remarkably, these expression changes are associated with specific alterations in H3K27me3, suggesting that Polycomb-mediated repression plays a role in precursor B cell ageing.

Conclusions: Components of the insulin-like growth factor signalling pathways are key targets of epigenetic regulation in ageing in bone marrow B cell precursors.
 
Overall design 12 total RNA-seq samples (rRNA-depleted; 3 replicates from pro-B and pre-B cells sorted from young and aged mice); 4 nuclear RNA-seq samples (2 replicates from pro-B cells sorted from young and aged mice); 16 microRNA-seq samples (4 replicates from pro-B and pre-B cells sorted from young and aged mice); 16 ATAC-seq samples (4 replicates from pro-B and pre-B cells sorted from young and aged mice); 4 CTCF ChIP-seq samples (2 replicates from pre-B cells sorted from young and aged mice); 8 H3K4me3 ChIP-seq samples (2 replicates from pro-B and pre-B cells sorted from young and aged mice); 8 H3K27me3 ChIP-seq samples (2 replicates from pro-B and pre-B cells sorted from young and aged mice); 4 H3K27ac ChIP-seq samples (1 sample from pro-B and pre-B cells sorted from young and aged mice); 4 Hi-C samples (2 replicates from pre-B cells sorted from young and aged mice); 4 Promoter Capture Hi-C samples (2 replicates from pre-B cells sorted from young and aged mice)
 
Contributor(s) Bolland DJ, Stellato C, Schoenfelder S, Koohy H, Matheson LS, Spivakov M, Fraser P, Corcoran AE, Varga-Weisz P
Citation(s) 30180872
Submission date Jan 25, 2018
Last update date Mar 21, 2019
Contact name Steven William Wingett
E-mail(s) steven.wingett@mrc-lmb.cam.ac.uk
Organization name MRC Laboratory of Molecular Biology
Department Cell Biology
Street address Francis Crick Avenue, Cambridge Biomedical Campus
City Cambridge
State/province Cambs
ZIP/Postal code CB2 0QH
Country United Kingdom
 
Platforms (2)
GPL15103 Illumina HiSeq 1000 (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (90)
GSM2948203 Total RNA-seq proB young 1
GSM2948204 Total RNA-seq proB young 2
GSM2948205 Total RNA-seq proB young 3
Relations
BioProject PRJNA431625
SRA SRP131401

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
GSE109671_ATAC_preB_MACS_counts.txt.gz 405.8 Kb (ftp)(http) TXT
GSE109671_ATAC_proB_MACS_counts.txt.gz 605.0 Kb (ftp)(http) TXT
GSE109671_CTCF_preB_MACS_counts.txt.gz 171.1 Kb (ftp)(http) TXT
GSE109671_H3K27ac_preB_MACS_counts.txt.gz 181.0 Kb (ftp)(http) TXT
GSE109671_H3K27ac_proB_MACS_counts.txt.gz 195.5 Kb (ftp)(http) TXT
GSE109671_H3K27me3_preB_MACS_counts.txt.gz 66.1 Kb (ftp)(http) TXT
GSE109671_H3K27me3_proB_MACS_counts.txt.gz 66.7 Kb (ftp)(http) TXT
GSE109671_H3K4me3_preB_MACS_counts.txt.gz 298.6 Kb (ftp)(http) TXT
GSE109671_H3K4me3_proB_MACS_counts.txt.gz 320.3 Kb (ftp)(http) TXT
GSE109671_HiC_AB_compartment_PCA_scores.txt.gz 185.4 Kb (ftp)(http) TXT
GSE109671_MicroRNA_counts.txt.gz 42.0 Kb (ftp)(http) TXT
GSE109671_Nuclear_RNA_counts.txt.gz 321.1 Kb (ftp)(http) TXT
GSE109671_PCHiC_interaction_scores.txt.gz 6.3 Mb (ftp)(http) TXT
GSE109671_Total_RNA_counts.txt.gz 559.7 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap