Gonzalez et al. 2014 (PRJNA223060)

General Details

Title Cell type-specific ribosome profiling in vivo.
Organism
Number of Samples 8
Release Date 2013/10/18 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP031501
ENA SRP031501
GEO
BioProject PRJNA223060

Publication

Title
Authors Gonzalez C,Sims JS,Hornstein N,Mela A,Garcia F,Lei L,Gass DA,Amendolara B,Bruce JN,Canoll P,Sims PA
Journal The Journal of neuroscience : the official journal of the Society for Neuroscience
Publication Date 2014 Aug 13
Abstract Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5'-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. Copyright © 2014 the authors 0270-6474/14/3410924-13$15.00/0.
PMC PMC4131009
PMID 25122893
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR1013478 PRJNA223060 Mus musculus
SRR1013479 PRJNA223060 Mus musculus
SRR1013480 PRJNA223060 Mus musculus
SRR1562539 PRJNA223060 Homo sapiens Ribo-Seq Cycloheximide
SRR1562540 PRJNA223060 Homo sapiens Ribo-Seq Cycloheximide
SRR1562541 PRJNA223060 Homo sapiens Ribo-Seq Cycloheximide
SRR1562542 PRJNA223060 Homo sapiens Ribo-Seq Cycloheximide
SRR1562543 PRJNA223060 Homo sapiens Ribo-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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