IPSC-NSCs-Derived Exosomal let-7b-5p Improves Motor Function After Spinal Cord Injury by Modulating Microglial/Macrophage Pyroptosis
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ABSTRACT:
PROVIDER: PRJNA1112753 | ENA |
REPOSITORIES: ENA
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Project description:Background: Following spinal cord injury (SCI), the inflammatory storm initiated by microglia/macrophages poses a significant impediment to the recovery process. Exosomes play a crucial role in the transport of miRNAs, facilitating essential cellular communication through the transfer of genetic material. However, the miRNAs from iPSC-NSCs-Exos and their potential mechanisms leading to repair after SCI remain unclear. This study aims to explore the role of iPSC-NSCs-Exos in microglia/macrophage pyroptosis and reveal their potential mechanisms. Methods: iPSC-NSCs-Exos were characterized and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. A mouse SCI model and a series of in vivo and in vitro experiments were conducted to investigate the therapeutic effects of iPSC-NSCs-Exos. Subsequently, miRNA microarray analysis and rescue experiments were performed to confirm the role of miRNAs in iPSC-NSCs-Exos in SCI. Mechanistic studies were carried out using Western blot, luciferase activity assays, and RNA-ChIP. Results: Our findings revealed that iPSC-NSCs-derived exosomes inhibited microglia/macrophage pyroptosis at 7 days post-SCI, maintaining myelin integrity and promoting axonal growth, ultimately improving mice motor function. The miRNA microarray showed let-7b-5p to be highly enriched in iPSC-NSCs-Exos, and LRIG3 was identified as the target gene of let-7b-5p. Through a series of rescue experiments, we uncovered the connection between iPSC-NSCs and microglia/macrophages, revealing a novel target for treating SCI. Conclusion: In conclusion, we discovered that iPSC-NSCs-derived exosomes can package and deliver let-7b-5p, regulating the expression of LRIG3 to ameliorate microglia/macrophage pyroptosis and enhance motor function in mice after SCI. This highlights the potential of combined therapy with iPSC-NSCs-Exos and let-7b-5p in promoting functional recovery and limiting inflammation following SCI.
2024-07-17 | GSE267739 | GEO
Project description:Sinorhizobium meliloti 7B Resequencing
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Project description:Using 270K Nimblegen Comparative Genomic Hybridization (CGH) array on a set of cv. Chinese Spring deletion lines, a total of 3,671 sequence contigs and scaffolds (~7.8% of chromosome 7B physical length) were mapped into nine deletion bins. In our study we have developed 270K CGH Nimblegen array containing wheat 7B chromosome specific probes and genotyped wheat 7B deletion stocks which have terminal deletions in 7B. Our main aim was to identify absent probes (sequences) in deletion lines. Initially, spatial normalization and M-A loess normalization was performed for comparison test/reference and then clustering analysis (Mcust) was carried out. Further analysis was done on scaffolds (i.e. on larger sequences instead of probes; probes are designed from scaffolds) Hybridization of DNA from 13 wheat lines, including 11 Chinese Spring cytogenetic stocks (Del7BL-9, DT7BL, DT7BS, Del7BL-13, Del7BL-14, Del7BL-5, Del7BL-1, Del7BL-7Del1DS-3, Del7BL-2,Del7BS-2, Del7BL-3) and 2 replicates of Langdon (LDN) tetraploid wheat. A set of 49,500 7B chromosome specific features (ISBP probes and random genomic features) and 18,000 control probes with each probe replicated four times on the 270K chip.
2014-05-09 | E-GEOD-57461 | biostudies-arrayexpress
Project description:Using 270K Nimblegen Comparative Genomic Hybridization (CGH) array on a set of cv. Chinese Spring deletion lines, a total of 3,671 sequence contigs and scaffolds (~7.8% of chromosome 7B physical length) were mapped into nine deletion bins. In our study we have developed 270K CGH Nimblegen array containing wheat 7B chromosome specific probes and genotyped wheat 7B deletion stocks which have terminal deletions in 7B. Our main aim was to identify absent probes (sequences) in deletion lines. Initially, spatial normalization and M-A loess normalization was performed for comparison test/reference and then clustering analysis (Mcust) was carried out. Further analysis was done on scaffolds (i.e. on larger sequences instead of probes; probes are designed from scaffolds)
2014-05-09 | GSE57461 | GEO
Project description:The 7B-1 tomato (Solanum lycopersicum L. cv Rutgers) is a male-sterile mutant with enhanced tolerance to abiotic stress, which makes it a potential candidate for hybrid seed breeding and stress engineering. Transcriptomic profiles of the 7B-1 male-sterile and wild type (WT) anthers were studied using mRNA sequencing (RNA-Seq). In total, 768 differentially expressed genes (DEGs) were identified, including 132 up-regulated and 636 down-regulated transcripts. Gene ontology (GO) enrichment analysis of DEGs suggested a general impact of the 7B-1 mutation on metabolic processes, such as proteolysis and carbohydrate catabolic process. Sixteen candidates with key roles in regulation of anther development were subjected to further analysis using qRT-PCR and in situ hybridization. Cytological studies showed several defects associated with anther development in the 7B-1 mutant, including unsynchronized anther maturation, dysfunctional meiosis, arrested microspores, defect in callose degradation and abnormal tapetum development. TUNEL assay showed a defect in programmed cell death (PCD) of tapetal cells in 7B-1 anthers. The present study provides insights into the transcriptome of the 7B-1 mutant. We identified several genes with altered expression level in 7B-1 (including beta-1,3 glucanase, GA2oxs, cystatin, cysteine protease, pectinesterase, TA29, and actin) that could potentially regulate anther developmental processes, such as meiosis, tapetum development, and cell-wall formation/degradation.
2017-02-09 | GSE85859 | GEO
Project description:Primitive neural stem cells (NSCs) could be derived from pluripotent mouse embryonic stem (ES) cells, and then differentiate into definitive-type neural stem cells which resemble NSCs obtained from the central nervous system. Hence, primitive NSCs define an early stage of neural induction and provide a model to understand the mechanism that controls initial neural commitment. In this study, we performed microarray assay to analyze the global transcriptional profiles in mouse ES cell-derived primitive and definitive NSCs and to depict the molecular changes during the multi-staged neural differentiation process. Primitive NSCs derived directly from ESCs in Lif (p-NSC_L), primitive NSCs that were sub-cultured in the presence of Lif and FGF (p-NSC_LF), as well as definitive NSCs derived from primitive NSCs in medium containing FGF and EGF, were collected for RNA extraction and hybridization on Affymetrix microarrays. Mouse ESCs and NSCs obtained from mouse embryonic brain (E11.5) were included for controls. For each cell type, we collected two biological replicate samples for microarray analysis.
2014-03-01 | E-GEOD-44608 | biostudies-arrayexpress
Project description:Modulating M1/M2 polarization is a potential therapy for treating ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) held the capacity to regulate astrocytic polarization, but little is known about rTMS effects on microglia. Therefore, the present study aimed to investigate whether and how rTMS influence microglia polarization in ischemic stroke models. The 10-Hz rTMS was applied to transient middle cerebral artery occlusion (MCAO) rats and oxygen and glucose deprivation/ reoxygenation injured BV2 cells. Western blot, immunofluorescence and ELISA were used to detect M1/M2 markers. High-throughput sequencing, RT-PCR and FISH staining were adopted to test microRNA changes. The 10-Hz rTMS inhibited ischemia/reperfusion induced M1 microglia and significantly increased let-7b-5p. HMGA2 was proved to be the target protein of let-7b-5p and its downstream NF-κB signaling pathway were inhibited by rTMS. Microglia culture medium (MCM) collected from rTMS treated microglia had low TNF-α but high IL-10 concentration, leading to reduced neural death, minor ischemic volumes and improved functional recovery of MCAO animals. However, knockdown of let-7b-5p by antagomir reversed rTMS effects on microglia. In conclusion, high-frequency rTMS could improve functional recovery through inhibiting M1 microglia polarization via regulating let-7b-5p/HMGA2/NF-κB signaling pathway in cerebral ischemic stroke models.
2022-08-10 | GSE192910 | GEO
Project description:Rhodococcus qingshengii strain:7B Genome sequencing
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Project description:Pyroptosis is a recently discovered form of lytic cell death that is characterized by cell swelling and formation of pores and large bubbles on the plasma membrane. We find radiation could induce pyroptosis in human colorectal cancer HCT116 cells, and irradiation induces pyroptosis in mouse normal intestine MODEK cells only after 36 hours and over 8.0 Gy. In view of the significant pyroptosis effect of MODE-K cells, we selected 4Gy and 12Gy, 24h and 48h for experiments. After ONT full-length transcriptome sequencing, the cell pyroptosis model can screen out the differential genes related to cell pyroptosis, which is helpful to further explore the mechanism of pyroptosis of MODE-K cells.
2024-08-01 | GSE211709 | GEO