Small RNA sequencing of small extracellular vesicles derived from human skeletal muscle cells during myogenic differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE347685 | GEO | 2026/09/22
REPOSITORIES: GEO
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Project description:Background: Sarcopenia is a common and progressive skeletal muscle disorder characterized by atrophic muscle fibers and contractile dysfunction. Accumulating evidence shows that the number and function of satellite cells (SCs) decline and become impaired during aging, which may contribute to impaired regenerative capacity. A series of myokines/ small extracellular vesicles (sEVs) released from muscle fibers regulate metabolism in muscle and extramuscular tissues in an autocrine/paracrine/endocrine manner during muscle atrophy. It is still unclear whether myokines/sEVs derived from muscle fibers can affect satellite cell function during aging. Methods: Aged mice were used to investigate changes in the myogenic capacity of SCs during aging-induced muscle atrophy. The effects of atrophic myotube-derived sEVs on satellite cell differentiation were investigated by biochemical methods and immunofluorescence staining. Small RNA sequencing was performed to identify differentially expressed sEV microRNAs (miRNAs) between the control myotubes and atrophic myotubes. The target genes of the miRNA were predicted by bioinformatics analysis and verified by luciferase activity assays. The effects of identified miRNA on the myogenic capacity of SCs in vivo were investigated by intramuscular injection of adeno-associated virus (AAV) to overexpress or silence miRNA in skeletal muscle. Results: Our study showed that the myogenic capacity of SCs was significantly decreased (50%, n = 6, P < 0.001) in the tibialis anterior muscle of aged mice. We showed that atrophic myotube-derived sEVs inhibited satellite cell differentiation in vitro (n = 3, P < 0.001) and in vivo (35%, n = 6, P < 0.05). We also found that miR-690 was the most highly enriched miRNA among all the screened sEV miRNAs in atrophic myotubes [Log2 (Fold Change) = 7, P<0.001], which was verified in the atrophic muscle of aged mice (3-fold, n = 6, P < 0.001) and aged humans (2.8-fold, n = 10, P < 0.001). miR-690 can inhibit myogenic capacity of SCs by targeting myocyte enhancer factor 2, including Mef2a, Mef2c, and Mef2d, in vitro (n=3, P < 0.05) and in vivo (n=6, P < 0.05). Specific silencing of miR-690 in the muscle can promote satellite cell differentiation (n = 6, P < 0.001) and alleviate muscle atrophy in aged mice (n = 6, P < 0.001). Conclusions: Our study demonstrated that atrophic muscle fiber-derived sEV miR-690 may inhibit satellite cell differentiation by targeting myocyte enhancer factor 2 during aging.
2022-12-21 | GSE211885 | GEO
Project description:Adipose-derived stem cells (ASCs) and their small extracellular vesicles (sEVs) hold significant potential for regenerative medicine due to their capabilities for tissue repair. However, the effects of ASC heterogeneity on sEV characteristics and microRNA (miRNA) profiles remain unclear. We investigated ASCs heterogeneity and its changes with aging and cell expansion using bulk RNA-seq from young and old donors across various passages. Non-negative matrix factorization (NMF) was used to identify distinct ASC clusters. Small RNA sequencing was performed on sEVs collected from ASC culture supernatants to analyze miRNA profiles. NMF analysis revealed ASC heterogeneity, identifying clusters characterized by ISLR and genes associated with collagen and smooth muscle cells. The miRNA profiles of sEVs matched these ASC clusters, showing variations based on donor age and cell expansion. Functional enrichment analysis suggested that these miRNAs may have distinct functional roles. Our findings show that ASC heterogeneity and sEV miRNA content are significantly influenced by donor age and cell expansion. These variations underscore the necessity of selecting specific ASC-derived sEVs.
2024-12-11 | GSE276164 | GEO
Project description:Small extracellular vesicles (sEVs) play a critical role in cardiac cell therapy by delivering molecular cargo and mediating cellular signaling. Among sEV cargo molecule types, microRNA (miRNA) is particularly potent and highly heterogenous. However, not all miRNAs in sEV are beneficial. Two previous studies utilizing computational modeling identified miR-192-5p and miR-432-5p as potentially deleterious in cardiac function and repair. Here, we show that knocking down miR-192-5p and miR-432-5p in cardiac c-kit+ cell-derived sEVs enhances the therapeutic capabilities of sEVs in vitro and in a rat in vivo model of cardiac ischemia reperfusion. miR-192-5p and miR-432-5p depleted CPC-sEVs enhance cardiac function by reducing fibrosis, enhancing mesenchymal stromal cell-like cell mobilization, and inducing macrophage polarization to the M2 phenotype. Knocking down deleterious miRNAs from sEV could be a promising therapeutic strategy for treatment of chronic myocardial infarction.
2022-12-31 | GSE196469 | GEO
Project description:Small extracellular vesicles (sEVs) are critical mediators of tumour–microenvironment communication, largely through the selective transfer of microRNAs (miRNAs) that reprogram recipient cells. Active miRNA sorting into sEVs depends on RNA‑binding proteins, sequence determinants and RNA modifications. Here, a functional interplay between the RBP SYNCRIP and N6‑methyladenosine (m6A) RNA methylation in controlling miRNA loading into hepatocellular carcinoma (HCC)‑derived sEVs has been disclosed. It is reported that i) METTL3‑dependent m6A modification is required for efficient binding of SYNCRIP to specific miRNAs, thereby enabling their selective incorporation into sEVs; ii) silencing of SYNCRIP markedly reshapes the sEV miRNA-cargo and impairs the ability of HCC‑derived sEVs to induce epithelial–mesenchymal transition (EMT) in non‑tumorigenic hepatocytes. Notably, iii) depletion of METTL3 produces an even stronger effect, indicating that m6A methylation represents an upstream and essential determinant of SYNCRIP‑mediated miRNA export. Mechanistically, the data identify SYNCRIP as an m6A‑dependent miRNA reader, adding epitranscriptomic regulation to sequence‑based miRNA sorting into sEVs. Functionally, disruption of this interaction attenuates sEV‑driven EMT and pro‑tumorigenic signalling. Collectively, these findings uncover a novel regulatory axis governing sEV miRNA cargo selection and highlight the m6A–SYNCRIP interplay as a potential therapeutic target to interfere with EV‑mediated tumour progression and metastasis.
2026-06-12 | GSE317620 | GEO
Project description:Compared to whole serum miRNAs, miRNAs in serum small extracellular vesicles (sEVs) are well protected form RNA enzymes, thus provide a consistent source of miRNA for disease biomarker detection. Serum sEVs and their miRNA cargos released by injured liver cells could be promising biomarkers for diagnosis of liver diseases. We were very interested to find out the effects of liver injury on serum extracellular vesicles as well as the small RNA components they transported, if there is any difference between acute and chronic injury. Study in this regard will help us to identify new serum biomarkers for liver injury, and to find out if there are specific markers for acute or chronic liver injury. To identify potential biomarker for liver injury based on serum sEVs miRNAs, we established the carbon tetrachloride (CCL4) induced acute and chronic liver injury mice model, and examined the dynamic changes of small RNA components, especially miRNAs, in serum sEVs.
2021-08-07 | E-MTAB-9462 | biostudies-arrayexpress
Project description:Chronic kidney disease (CKD) accelerates vascular calcification (VC) via phenotypic switching of vascular smooth muscle cells (VSMCs). We investigated the roles of circulating small extracellular vesicles (sEVs) between the kidneys and VSMCs and uncovered relevant sEV-propagated microRNAs (miRNAs) and their biological signaling pathways. We established CKD models in rats and mice by adenine-induced tubulointerstitial fibrosis. The miRNA transcriptome of sEVs revealed a depletion of several miRNAs in CKD. Their expression levels in sEVs from CKD patients were correlated to kidney function. This study revealed the transcriptomic landscape of miRNAs propagated in sEVs in CKD. We investigated the therapeutic potential of miRNAs in VC.
2022-12-31 | GSE217558 | GEO
Project description:LoVo cells were cultured in sEV-depleted (160,000xg, 16h) complete medium and the supernatant were collected after 72h. sEVs were purified and centrifuged at 100,000xg for 2.5h using a Beckman SW41Ti rotor to know the miRNA in LoVo cells and LoVo-Small Extracellular Vesicles
2019-07-01 | GSE117866 | GEO
Project description:Adipose-derived stem cells (ASCs) and their small extracellular vesicles (sEVs) hold significant potential for regenerative medicine due to their capabilities for tissue repair. However, the effects of ASC heterogeneity on sEV characteristics and microRNA (miRNA) profiles remain unclear. We investigated ASCs heterogeneity and its changes with aging and cell expansion using bulk RNA-seq from young and old donors across various passages. Non-negative matrix factorization (NMF) was used to identify distinct ASC clusters. Small RNA sequencing was performed on sEVs collected from ASC culture supernatants to analyze miRNA profiles. NMF analysis revealed ASC heterogeneity, identifying clusters characterized by ISLR and genes associated with collagen and smooth muscle cells. The miRNA profiles of sEVs matched these ASC clusters, showing variations based on donor age and cell expansion. Functional enrichment analysis suggested that these miRNAs may have distinct functional roles. Our findings show that ASC heterogeneity and sEV miRNA content are significantly influenced by donor age and cell expansion. These variations underscore the necessity of selecting specific ASC-derived sEVs.
2024-12-11 | GSE276163 | GEO
Project description:Brain cells release and take up small extracellular vesicles (sEVs) containing bioactive nucleic acids. sEV exchange is hypothesized to contribute to stereotyped spread of neuropathological changes in the diseased brain. We assessed mRNA from sEVs of non-diseased (ND) and Alzheimer’s disease (AD) human postmortem brain, using short- and long-read sequencing. sEV transcriptomes were distinct from bulk tissue, showing enrichment for multiple genes including mRNAs encoding ribosomal proteins and L1Hs transposable elements. AD versus ND sEVs showed enrichment of inflammation-related and depletion of synaptic signaling mRNAs. sEV mRNA from cultured murine primary neurons, astrocytes, or microglia showed similarities with human brain sEVs and revealed cell-type specific packaging. Nearly 80% of human brain sEV transcripts sequenced using long-read sequencing were full-length. Motif analyses of sEV-enriched full-length isoforms revealed RNA-binding proteins that may be associated with sEV loading. Collectively, we show that mRNA in brain sEVs is selectively-packaged and altered by disease state.
2024-03-14 | GSE243611 | GEO
Project description:Brain cells release and take up small extracellular vesicles (sEVs) containing bioactive nucleic acids. sEV exchange is hypothesized to contribute to stereotyped spread of neuropathological changes in the diseased brain. We assessed mRNA from sEVs of non-diseased (ND) and Alzheimer’s disease (AD) human postmortem brains, using short- and long-read sequencing. sEV transcriptomes were distinct from bulk tissue, showing enrichment for multiple genes including mRNAs encoding ribosomal proteins and L1Hs transposable elements. AD versus ND sEVs showed enrichment of inflammation-related and depletion of synaptic signaling mRNAs. sEV mRNA from cultured murine primary neurons, astrocytes, or microglia showed similarities with human brain sEVs and revealed cell-type specific packaging. Nearly 80% of human brain sEV transcripts sequenced using long-read sequencing were full-length. Motif analyses of sEV-enriched full-length isoforms revealed RNA-binding proteins that may be associated with sEV loading. Collectively, we show that mRNA in brain sEVs is selectively-packaged and altered by disease state.
2024-03-14 | GSE255462 | GEO