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SRX3723695: GSM3017992: PR5 BTSC; Mus musculus; RNA-Seq
2 ILLUMINA (Illumina HiSeq 2000) runs: 52.9M spots, 1.6G bases, 1.1Gb downloads

Submitted by: NCBI (GEO)
Study: Identification and validation of GPD1 as an essential cancer stem cell specific target in glioblastoma (Ribosome profiling)
show Abstracthide Abstract
Cancer stem cells (CSCs) are attractive targets for cancer therapy, however, little is known about how to target CSCs without affecting the normal stem cell population. Here we report the ribosome-profiling analysis of mouse neural stem cells and brain tumour stem cells (BTSCs), which leads to the identification of glycerol-3-phosphate dehydrogenase 1 (GPD1) as a CSC- specific determinant. We confirmed that GPD1 is expressed in BTSCs but not in neural stem cells. Intriguingly, expression of GPD1 is only found in the infiltrating dormant BTSCs in vivo and these cells start to divide and drive tumour relapse after chemotherapy. Most importantly, inhibition of GPD1 expression in tumour-bearing mice leads to prolonged survival. Further analysis shows that loss of GPD1 results in widespread changes in important pathways affecting BTSC maintenance. Human patient data analysis suggests that GPD1 is expressed in the dormant infiltrating tumour cells in human glioblastoma and the expression level is associated with a worse prognosis. This study provides an attractive therapeutic target for treating brain tumours and a novel aspect of regulation of CSC dormancy. Overall design: Two neural stem cell samples and three brain tumor stem cell samples are used in ribosome profiling experiments.
Sample: PR5 BTSC
SAMN08567967 • SRS2981012 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: Illumina HiSeq 2000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: SINGLE
Construction protocol: The cells of a 15 cm culture plate were lysed with lysis buffer (20 mM Tris-HCl pH 7.4, 10 mM MgCl2, 200 mM KCl, 1 % Triton, 2 mM DTT, 100 µg/ml Cyclohexamide, 25 U/ml DNase and EDTA-free protease inhibitors, Roche). The mRNA not protected by ribosomes was digested with RNAseI and the ribosome footprints were collected by centrifugation with a continuous sucrose gradient (10-50 %) with DTT, cyclohexamideand 20 U/ml SUPERaseIN. The fraction with the ribosome footprint RNA was used for acid phenol extraction. Precipitated RNA was resuspended in 10 mM Tris pH7, mixed with 2x sample buffer (TBE-urea, NOVEX, Invitrogen) and loaded on a 15 % TBE-urea gel. The region between 26-34 nt was excised and used for library generation exactly as described previously (Ingolia et al, Nat Protoc 2012). The library was sequenced on the Illumina HiSeq system according to the manufacturer's protocol.
Experiment attributes:
GEO Accession: GSM3017992
Links:
Runs: 2 runs, 52.9M spots, 1.6G bases, 1.1Gb
Run# of Spots# of BasesSizePublished
SRR675108126,404,316775.4M559.6Mb2019-07-16
SRR675108226,517,962778.7M560.4Mb2019-07-16

ID:
5137389

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