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Series GSE31574 Query DataSets for GSE31574
Status Public on Dec 31, 2014
Title Genome-wide expression analysis of self renewing hematopoietic stem cells (HSC) in control and CD70TG mice.
Organism Mus musculus
Experiment type Expression profiling by array
Summary To study the effect of CD27 triggering on HSC biology
Ageing of the hematopoietic stem cell (HSC) compartment is characterized by an accumulation of less productive HSCs with impaired lymphoid differentiation capacity, which contributes to age-dependent hematological abnormalities including anemia, myeloproliferative disorders and a decline in adaptive immunity. Since HSCs express the costimulatory receptor CD27 and because inflammation has been associated with HSC ageing, we investigated the effect of stimulation of CD27 by its inflammatory ligand CD70 on HSC maintenance. We found that CD27-triggering during CD70-driven immune activation in young mice enhances HSC self-renewal, leading to accumulation of HSCs to levels comparable with old control mice. These findings indicate that CD27-signaling accelerates HSC ageing, which is supported by the observation that CD27-triggering negatively affects HSC differentiation to the lymphoid lineage and increases myeloid differentiation. This functional change was mirrored by a corresponding difference in gene expression, as microarray analysis indicated that CD27-triggered HSCs have a strongly myeloid-biased gene signature. CD27 signaling also induced enrichment of genes associated with biological processes involved in cellular responses to DNA damage/repair and reactive oxygen species (ROS), which are associated with HSC ageing and related to increased proliferation. Therefore, we postulate that CD27 triggering during chronic inflammation contributes directly to ageing of the hematopoietic compartment.
Overall design FACS sorted fractions of long term (CD34-) and short-term (CD34+) HCS from control (IFNgamma-/-) and CD70TG (IFNgamma-/-xCD70TG) mice. RNA from two mice was pooled on each microarray and 4 independent replicates were used per condition.
Contributor(s) de Bruin AM, 't Hoen PA, Nolte MA
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Submission date Aug 22, 2011
Last update date Jun 14, 2018
Contact name Peter A.C. 't Hoen
Phone +31 71 5269421
Fax +31 71 5268285
Organization name Leiden University Medical Center
Department Center for Human and Clinical Genetics
Street address PO Box 9600
City Leiden
ZIP/Postal code 2300 RC
Country Netherlands
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (16)
GSM783865 control_CD34Neg_1
GSM783866 CD70Tg_CD34Neg_1
GSM783867 control_CD34Neg_2
BioProject PRJNA145669

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
GSE31574_RAW.tar 3.1 Mb (http)(custom) TAR
GSE31574_non-normalized.txt.gz 2.7 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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