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Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control

ABSTRACT: Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control

PROVIDER: PRJNA915107 | ENA |

REPOSITORIES: ENA

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Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (scRNA-Seq)

Project description:Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.

2024-10-08 | GSE221642 | GEO

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Ribo-Seq)

2024-10-08 | GSE221640 | GEO

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Polysome-Seq)

2024-10-08 | GSE221639 | GEO

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (RNA-Seq)

2024-10-08 | GSE221641 | GEO

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Polysome-Seq)

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Polysome-Seq)

| PRJNA915109 | ENA

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Ribo-Seq)

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Ribo-Seq)

| PRJNA915110 | ENA

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (scRNA-Seq)

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (scRNA-Seq)

| PRJNA915112 | ENA

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (RNA-Seq)

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (RNA-Seq)

| PRJNA915111 | ENA

Spermidine is essential for fasting-mediated autophagy and longevity

Project description:Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health 1. The natural polyamine spermidine has been linked to autophagy regulation, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders 2. Here, we report that spermidine levels increase upon acute fasting in yeast, flies, mice and healthy humans. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, worms and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan-extending, cardioprotective and antiarthritic effects of intermittent fasting. Mechanistically, spermidine mediated these effects via hypusination of the autophagy regulator eIF5A. In sum, the polyamine-hypusination axis thus emerges as a bona fide and phylogenetically conserved metabolic control hub for longevity and autophagy induction.

2024-04-30 | PXD035909 | Pride

YAP/TAZ drives cell proliferation and tumour growth via a polyamine-eIF5A hypusination-LSD1 axis

Project description:Here using mouse genetic models and human cancer cells, we show that YAP/TAZ reprogram polyamine metabolism to promote cell proliferation and tumor growth. Mechanistically, YAP/TAZ increases polyamine synthesis mainly through direct upregulation of the major rate-limiting enzyme ornithine decarboxylase 1. We further demonstrate that the polyamine spermidine sustains eukaryotic translation factor 5A (eIF5A) hypusination to support efficient translation of histone demethylase LSD1 that maintains a favored epigenetic status for YAP/TAZ-induced cell proliferation. Furthermore, inhibiting either polyamine synthesis or LSD1 can suppress YAP/TAZ-induced cell proliferation in mouse liver and human cancer cells. Thus our study identifies a YAP/TAZ-polyamine-eIF5A hypusination-LSD1 axis as required for YAP/TAZ-induced cell proliferation and tumor growth and suggests LSD1 as a critical target of polyamine in tumorigenesis.

2022-01-01 | GSE174041 | GEO

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