Elevated Extracellular Purine Nucleotides Impair Muscle Regeneration in Diabetic Mice by Suppressing Early Activation of Muscle Satellite Cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA733661 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14684934_1.fastq.gz | Fastqsanger.gz | |||
| SRR14684934_2.fastq.gz | Fastqsanger.gz | |||
| SRR14684935_1.fastq.gz | Fastqsanger.gz | |||
| SRR14684935_2.fastq.gz | Fastqsanger.gz | |||
| SRR14684936_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:Chronic diabetic patients often exhibit defective tissue repair. Similarly, injury-induced muscle regeneration was also found to be defective in diabetic mice. However, the underlying mechanisms remain obscure. Here, we found that quiescent muscle satellite cells (MuSC) from db/db diabetic mice, a mouse model for obesity-induced type 2 diabetes, failed to re-enter the cell cycle upon activation in vivo but not in culture, suggesting the involvement of certain niche factors. Elevated extracellular AMP (eAMP) and adenosine (eAdo) were detected in both muscle tissues and blood of diabetic patients and mice. Unexpectedly, we found that eAMP and eAdo potently inhibited cell cycle re-entry of MuSC, and consequently impaired injury-induced muscle regeneration. Mechanistically, we demonstrated that eAMP and eAdo impaired the functions of MuSC via a signaling axis of equilibrative Ado transporter (ENT)-Ado kinase (ADK)-AMPK, which in turn inhibited an mTORC1-dependent cell growth checkpoint and subsequent cell cycle re-entry. Moreover, eAdo also inhibited early activation of quiescent fibroadipogenic progenitors and human MuSC by the same mechanism. Importantly, treatment of db/db diabetic mice with an ADK inhibitor not only reduced plasma glucose level but also partially restored the regenerative functions of MuSC in vivo. Collectively, our study suggests that both ENT and ADK are promising therapeutic targets for the treatment of diabetes and for restoring the regenerative functions of tissue stem cells.
2022-05-28 | GSE175786 | GEO
Project description:Skeletal muscle fiber type distribution has implications for human health, muscle function and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. This data was used to present a new method based on muscle tissue RNA sequencing data to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for larger number of individuals to be tested in a cost and labor efficient way. Muscle biopsies were taken from the vastus lateralis muscle of 39 Swedish male subjects. Samples were sequenced on the NextSeq® 500/550 (Illumina).
| EGAS00001006363 | EGA
Project description:A variety of epigenetic alterations impairs functions of cells and tissues during aging, but it is not known if epigenetic alterations are associated with aging muscle. Here, we examined the changes of a panel of histone marks and found H3K27ac (an active enhancer mark) is markedly increased during aging in human skeletal muscle tissues. Our integrated analysis showed that enhancer activation during muscle aging is associated with the up-regulation of extracelluar matrix (ECM) genes, which may result in stiffness of the niche environment of satellite cells (SCs). An age-related fibrogenic conversion of geriatric SCs was observed through differential gene expression analysis. In mice, treatment of aging muscles with JQ1, an inhibitor of enhancer activation reverted the ECM up-regulation and fibrogenic conversion of SCs, suggesting that ECM increase in aging muscle is indeed a result of enhancer activation. The study here not only uncovered a novel aspect of muscle aging that is associated with enhancer remodeling but also highlighted JQ1 as a potential treatment approach for restoring SC function in aging muscle.
2019-08-15 | GSE122867 | GEO
Project description:The libraries contained in this experiment come from skeletal muscle myosatellite cells isolated from independent donors. They are stranded PE101 Illumina Hi-Seq RNA-Seq libraries from rRNA-depleted Total RNA > 200 nucleotides in size. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2016-03-18 | GSE78611 | GEO
Project description:Synthesized DNA with unnatural nucleotides Synthetic Genomics
| PRJNA89669 | ENA
Project description:The ability of Leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. However, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. To elucidate nutrient stress response pathways in Leishmania donovani, we have used purine starvation as the paradigm. The salvage of purines from the host milieu is obligatory for parasite replication; nevertheless, purine-starved parasites can persist in culture without supplementary purine for over 3 months, indicating that the response to purine starvation is robust and engenders parasite survival under conditions of extreme scarcity. To understand metabolic reprogramming during purine starvation we have employed global approaches. Whole proteome comparisons between purine-starved and purine-replete parasites over a 6-48 h span have revealed a temporal and coordinated response to purine starvation. Purine transporters and enzymes involved in acquisition at the cell surface are upregulated within a few hours of purine removal from the media, while other key purine salvage components are upregulated later in the time-course and more modestly. After 48 h, the proteome of purine-starved parasites is extensively remodeled and adaptations to purine stress appear tailored to deal with both purine deprivation and general stress. To probe the molecular mechanisms affecting proteome remodeling in response to purine starvation, comparative RNA-seq analyses, qRT-PCR, and luciferase reporter assays were performed on purine-starved versus purine-replete parasites. While the regulation of a minority of proteins tracked with changes at the mRNA level, for many regulated proteins it appears that proteome remodeling during purine stress occurs primarily via translational and post-translational mechanisms. One mRNA sample from each of Purine-Starved and Purine-Replete cells were analyzed using SL RNA-Seq methodology
2014-02-01 | E-GEOD-48394 | biostudies-arrayexpress
Project description:The effect of nucleotides on the intestinal microbiota of zebrafish
| PRJEB19156 | ENA
Project description:Purpose:To investigate the transcriptomic profiles in zebrafish embryos exposed externally to nucleotides at a critical develpomental window (3-7 days post fertilization) determine biological processes and pathways based on differentially expressed gene transcripts using High Throughput Sequencing (HTS). Methods:Total mRNA profiles of 7 dpf zebraifsh embryos after exposure to 10-5M ATP, AMP, adenosine and adenine were generated by deep sequencing, in triplicate, using Illumina HiSeq2500 Results: There were many differentially expressed genes; including ubiquitin-, actin-, and tubulin-related, showing that the cytoskeleton was altered; other DEGs involved with purine binding, specifically guanine, which was expected as the mixture was composed of purines; DEGs involved with GTP binding were also upregulated, suggesting increased cell signaling,
2020-03-23 | GSE97016 | GEO
Project description:The ability of Leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. However, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. To elucidate nutrient stress response pathways in Leishmania donovani, we have used purine starvation as the paradigm. The salvage of purines from the host milieu is obligatory for parasite replication; nevertheless, purine-starved parasites can persist in culture without supplementary purine for over 3 months, indicating that the response to purine starvation is robust and engenders parasite survival under conditions of extreme scarcity. To understand metabolic reprogramming during purine starvation we have employed global approaches. Whole proteome comparisons between purine-starved and purine-replete parasites over a 6-48 h span have revealed a temporal and coordinated response to purine starvation. Purine transporters and enzymes involved in acquisition at the cell surface are upregulated within a few hours of purine removal from the media, while other key purine salvage components are upregulated later in the time-course and more modestly. After 48 h, the proteome of purine-starved parasites is extensively remodeled and adaptations to purine stress appear tailored to deal with both purine deprivation and general stress. To probe the molecular mechanisms affecting proteome remodeling in response to purine starvation, comparative RNA-seq analyses, qRT-PCR, and luciferase reporter assays were performed on purine-starved versus purine-replete parasites. While the regulation of a minority of proteins tracked with changes at the mRNA level, for many regulated proteins it appears that proteome remodeling during purine stress occurs primarily via translational and post-translational mechanisms.
2014-02-01 | GSE48394 | GEO
Project description:Elevated H3K27ac in aged skeletal muscle tissue drives a fibrogenic conversion of muscle satellite cells
| PRJNA506722 | ENA