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Series GSE56275 Query DataSets for GSE56275
Status Public on Jul 31, 2014
Title Gene expression differences between prion-resistant and prion-susceptible cells
Organism Mus musculus
Experiment type Expression profiling by array
Summary Prions consist of aggregates of abnormal conformers of cellular prion protein (PrPC). They propagate by recruiting host-encoded PrPC although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrPC expression differences, to identify such factors. We examined the transcriptomes of prion-resistant revertants, isolated from highly susceptible cells, and identified a gene expression signature associated with susceptibility. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP deposits. Loss-of-function of nine of these genes significantly increased susceptibility. Remarkably, inhibition of fibronectin 1 binding to integrin α8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation rates. This indicates that prion replication may be controlled by MMPs at the ECM in an integrin-dependent manner.
 
Overall design For each of the three biological repeats cell clones (samples) were harvested at a subclonfluent state and total RNA isolated using Rneasy (Qiagen) according to the specification of the manufacturer. Retinoic acid treatment of revertant cell clones (R2, R5, R7) increased prion replication by up to fourty-fold. To test differential gene expression under these conditions R7 cells were treated with retinoic acid (0.5 microM) and vehicle for six hours, before isolation of total RNA as described previously (PK 11.1 210307, PK 11.3 210307,PK 13.1 210307,PK 13.2 210307,PK 13.3 210307)
 
Contributor(s) Marbiah M, Harvey A, West B, Louzolo A, Banerjee P, Alden J, Grigoriadis A, Jat P, Hummerich H, Kan H, Cai Y, Bloom GS, Collinge J, Klöhn P
Citation(s) 24843046
Submission date Mar 27, 2014
Last update date Feb 11, 2019
Contact name Peter Christian Kloehn
E-mail p.kloehn@prion.ucl.ac.uk
Phone +44 7717223537
Organization name UCL Institute of Neurology
Department MRC Prion Unit
Street address Queen Square
City London
State/province Greater London
ZIP/Postal code WC1N 3BG
Country United Kingdom
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (41)
GSM1358076 PK1-subconfluent-rep1
GSM1358077 PK1-subconfluent-rep2
GSM1358078 PK1-subconfluent-rep3
Relations
BioProject PRJNA242814

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
GSE56275_RAW.tar 150.3 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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