Satellite cell expansion is mediated by P-eIF2α-dependent Tacc3 translation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA691923 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13429048_1.fastq.gz | Fastqsanger.gz | |||
| SRR13429048_2.fastq.gz | Fastqsanger.gz | |||
| SRR13429049_1.fastq.gz | Fastqsanger.gz | |||
| SRR13429049_2.fastq.gz | Fastqsanger.gz | |||
| SRR13429050_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Translational control of gene expression is an important regulator of adult stem cell quiescence, activation and self-renewal. In skeletal muscle, quiescent satellite cells maintain low levels of protein synthesis, mediated in part through the phosphorylation of eIF2α (P-eIF2α). Pharmacological inhibition of the eIF2α phosphatase with the small molecule sal003 maintains P-eIF2α and permits the expansion of satellite cells ex vivo. Paradoxically, P-eIF2α also increases the translation of specific mRNAs, which is mediated by P-eIF2α-dependent read-through of inhibitory upstream open reading frames (uORFs). Here, we ask whether P-eIF2α-dependent mRNA translation enables expansion of satellite cells. Using transcriptomic and proteomic analyses, we show a number of genes associated with the assembly of the spindle pole to be upregulated at the level of protein, without corresponding change in mRNA levels, in satellite cells expanded in the presence of sal003. We show that uORFs in the 5′ UTR of mRNA for the mitotic spindle stability gene Tacc3 direct P-eIF2α-dependent translation. Satellite cells deficient for TACC3 exhibit defects in expansion, self-renewal and regeneration of skeletal muscle.
2021-01-14 | GSE164774 | GEO
Project description:We recently identified ISRIB as a potent inhibitor of the integrated stress response (ISR). ISRIB renders cells resistant to the effects of eIF2α phosphorylation and enhances long-term memory in rodents (10.7554/eLife.00498). Here we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2α and induced no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2α phosphorylation, SG formation and cognitive loss. Ribosome profiling with paired RNA-seq
2015-02-27 | E-GEOD-65778 | biostudies-arrayexpress
Project description:The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis. The data set contains one microarray of pooled quiescent skeletal muscle satellite cells
2014-07-11 | E-GEOD-59272 | biostudies-arrayexpress
Project description:We recently identified ISRIB as a potent inhibitor of the integrated stress response (ISR). ISRIB renders cells resistant to the effects of eIF2α phosphorylation and enhances long-term memory in rodents (10.7554/eLife.00498). Here we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2α and induced no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2α phosphorylation, SG formation and cognitive loss.
2015-02-27 | GSE65778 | GEO
Project description:The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis.
2014-07-11 | GSE59272 | GEO
Project description:To examine the relationship between protein synthesis and energy homeostasis, we created the whole body eIF2α haploinsufficient mouse model to establish a constantly reduced translation state.
2022-03-01 | GSE146160 | GEO
Project description:Local protein synthesis is rapidly regulated by extrinsic signals during neural wiring but the translational control mechanisms remain elusive. Here, we show that the guidance cue Sema3A, but not Slit1, elicits precise spatiotemporal control of the phosphorylation of the translation initiation factor, eIF2α, in axonal growth cones via the Unfolded Protein Response (UPR) kinase PERK. Strikingly, in contrast to the canonical UPR signaling, we find that the Sema3A-induced eIF2α phosphorylation bypasses the conventional global translational repression and underlies a burst in axonal protein synthesis, mediated by differential eIF2B activity. Ultrasensitive proteomics on somaless axons reveals a subset of 75 proteins translationally regulated via Sema3A-p-eIF2α, including several proteostasis- and actin cytoskeleton-related nascent proteins. Finally, in vivo experiments provide evidence that eIF2α phosphorylation drives the formation of the retinotectal axon projection. Thus, specific extracellular cues can trigger non-canonical PERK-eIF2α-eIF2B signaling leading to subcellular dynamic remodeling of the nascent proteome required for neural wiring.
2019-01-02 | PXD009250 | Pride
Project description:In yeast and mammals, activated GCN2 can phosphorylate its substrate eIF2α, which is a part of the eIF2-GTP-Met-tRNAiMet ternary complex. The eIF2α phosphorylation blocks the ternary complex formation and therefore inhibits translation initiation. Meanwhile, GCN2 activation associates with ribosomes and some translation elongation factors such as eEF1A. In Neurospora crassa, the homolog of GCN2 is CPC-3. Ribosome profiling and accompanying RNA-seq experiments in this project were used to explore the effects of CPC-3 on translation kinetics. Here we show that poor codon usage of mRNAs with long CDS preferentially causes CPC-3 activation, which in turn suppresses the translation initiation and elongation in both codon usage and CDS length dependent manner.
2021-08-10 | GSE168595 | GEO
Project description:The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2αbecomes phosphorylated, engendering a dramatic change in mRNA translation. The activation of ISR plays a pivotal role in the early embryogenesis but the eIF2-dependent translational landscape in pluripotent embryonic stem cells (ESC) is largely unexplored. We employ a multi-omics approachconsisting of ribosome profiling, proteomics, and metabolomics inwild-type(eIF2α+/+)andphosphorylation-deficient mutant eIF2α(eIF2αA/A)mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naïve pluripotency. We show a transient increase in p-eIF2α in the naïve epiblast layer of E4.5 embryos. Absence of eIF2α phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3α/β) withdrawal. p-eIF2α controls translation of mRNAs encoding proteins which govern pluripotency, chromatin organization, and glutathione synthesis.Thus, p-eIF2αacts as a key regulator of the naïve pluripotency gene regulatory network.
2023-12-29 | GSE248725 | GEO
Project description:The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2αbecomes phosphorylated, engendering a dramatic change in mRNA translation. The activation of ISR plays a pivotal role in the early embryogenesis but the eIF2-dependent translational landscape in pluripotent embryonic stem cells (ESC) is largely unexplored. We employ a multi-omics approachconsisting of ribosome profiling, proteomics, and metabolomics inwild-type(eIF2α+/+)andphosphorylation-deficient mutant eIF2α(eIF2αA/A)mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naïve pluripotency. We show a transient increase in p-eIF2α in the naïve epiblast layer of E4.5 embryos. Absence of eIF2α phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3α/β) withdrawal. p-eIF2α controls translation of mRNAs encoding proteins which govern pluripotency, chromatin organization, and glutathione synthesis.Thus, p-eIF2αacts as a key regulator of the naïve pluripotency gene regulatory network.
2023-12-29 | GSE248724 | GEO