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Series GSE254472 Query DataSets for GSE254472
Status Public on Jan 31, 2024
Title 4E-BP1-dependent translation in microglia controls mechanical hypersensitivity
Organism Mus musculus
Experiment type Other
Summary Spinal microglia play a pivotal role in the development of neuropathic pain. Peripheral nerve injury induces changes in the transcriptional profile of microglia, including increased expression of components of translational machinery. Whether microglial protein synthesis is stimulated following nerve injury and has a functional role in mediating pain hypersensitivity is unknown. Here, we show that nascent protein synthesis is upregulated in spinal microglia following peripheral nerve injury. Stimulating mRNA translation in microglia, via selective ablation of the translational repressor, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), promoted the transition of microglia to a reactive state and induced mechanical hypersensitivity. Conversely, inhibiting microglial translation by expressing mutant 4E-BP1 in microglia attenuated their peripheral nerve injury-induced activation and alleviated neuropathic pain. Thus, the stimulation of 4E-BP1-dependent translation promotes microglia reactivity and mechanical hypersensitivity, whereas its inhibition alleviates neuropathic pain.
 
Overall design Ablation of 4E-BP1 stimulates translation of eIF4E-sensitive mRNAs, which are involved in immune responses, modulation of extracellular matrix, cell survival and growth. To better understand how 4E-BP1 ablation affects microglial functions and induces mechanical pain hypersensitivity, we studied changes in the translational landscape in microglia lacking 4E-BP1. To identify the actively translating mRNAs in microglia, we employed a translating ribosome affinity purification (TRAP) approach . In TRAP, a ribosomal subunit L10a tagged with eGFP (L10a-eGFP) is expressed in a specific cell type. Immunoprecipitation (IP) with eGFP antibody captures the eGFP-tagged ribosomes and subsequent sequencing of immunoprecipitated ribosome-bound mRNAs allows the identification of actively translated mRNAs in the specific cell type.
 
Contributor(s) Khoutorsky A
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BioProject PRJNA1068585
Submission date Jan 29, 2024
Last update date Feb 01, 2024
Contact name Arkady Khoutorsky
E-mail(s) arkady.khoutorsky@mail.mcgill.ca
Organization name McGill University
Street address 3655 Promenade Sir-William-Osler
City Montreal
State/province Quebec
ZIP/Postal code H3G 1Y6
Country Canada
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM8042861 TMEM119 Control BL 1 IN
GSM8042862 TMEM119 Control BL 2 IN
GSM8042863 TMEM119 Control BL 3 IN

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Supplementary file Size Download File type/resource
GSE254472_RAW.tar 191.2 Mb (http)(custom) TAR (of GTF)
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Raw data are available in SRA

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