TsRNAs Are Potential Biomarkers of Acute Rejection in Vascularized Composite Allotransplantation
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ABSTRACT:
PROVIDER: PRJNA785574 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17096853.fastq.gz | Fastqsanger.gz | |||
| SRR17096854.fastq.gz | Fastqsanger.gz | |||
| SRR17096855.fastq.gz | Fastqsanger.gz | |||
| SRR17096856.fastq.gz | Fastqsanger.gz | |||
| SRR17096857.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: to explore the function and mechanism of acute rejection in vascularized composite allotransplantation Method: tRF & tiRNA profiles of acute rejection in vascularized composite allotransplantation were generated by deep sequencing, using Illumina NextSeq 500. qRT–PCR validation was performed using SYBR Green assays. Results:Sequencing was used to screen expression profiles and predict target genes. Compared with the control group, there were significant differences in the expression levels of 16 tRFs & tiRNAs, including 5 up-regulated target genes and 11 down-regulated target genes. Bioinformatics analysis and RT-qPCR revealed potential up regulation of tRFs & tiRNAs(tiRNA-1-33-Gly-GCC-1, tiRNA-1-34-Glu-CTC-1, tRF-1-32-Gly-GCC-2-M2) and down regulation of tRFs & tiRNAs (tRF-59:75-Gln-CTG-2-M2, tRF-59:76-Val-AAC-1-M2). Conclusion: In conclusion, it is speculated that tiRNA-1-34-Glu-CTC-1 plays an important role in VCA induced acute rejection by regulating CACNA1D gene in MAPK signaling pathway. This provides a new insight into the mechanism and therapeutic targets of acute rejection.
2022-07-20 | GSE190008 | GEO
Project description:A novel model for chronic rejection in vascularized composite allotransplantation identifies CXCL9-11 as potential biomarkers
| PRJNA552798 | ENA
Project description:Sentinel flaps are used for remote-site monitoring in vascularized composite allotransplantation (VCA), but their molecular relationship to facial allografts during rejection has not been defined. We analyzed gene expression in formalin-fixed paraffin-embedded (FFPE) skin biopsies from facial allografts (FA) and sentinel flaps (SF) obtained from five face transplant recipients at Brigham and Women’s Hospital. Simultaneous 4-mm punch biopsies were collected from FA and SF sites during grade 0 (non-rejection) and grade 3 (acute rejection) episodes, yielding 14 matched pairs. RNA was extracted and profiled using the NanoString nCounter PanCancer Immune Profiling Panel (730 immune-related genes). Data were normalized to positive controls and housekeeping genes using NanoString nSolver v4.0. Differentially expressed genes were identified by comparing grade 3 versus grade 0 samples in FA and SF separately. These datasets provide transcriptional profiles of acute rejection in human face transplants and sentinel flaps for use in comparative and mechanistic studies.
2025-12-10 | GSE313108 | GEO
Project description:Global mRNA expression profiling of transplanted rat hindlimbs (muscle and skin) were collected using Agilent rat whole genome array (Agilent-028282 Whole Rat Genome Microarray 4x44K v3). Hind limb transplantation between Fischer344 (donor) and Lewis (recipient) rats were performed. Isogenic transplantations served as controls. Administration of irregular immunosuppression induced chronic rejection. At the endpoint (post-operativ day 100), hind limbs presented clinicial, histomorphological and genetic changes, known to be highly suspicious for chronic rejection.
2020-07-02 | GSE133843 | GEO
Project description:BackgroundChronic rejection remains the Achilles heel in vascularized composite allotransplantation. Animal models to specifically study chronic rejection in vascularized composite allotransplantation do not exist so far. However, there are established rat models to study chronic rejection in solid organ transplantation such as allogeneic transplantation between the rat strains Lewis and Fischer344. Thus, we initiated this study to investigate the applicability of hindlimb transplantation between these strains to imitate chronic rejection in vascularized composite allotransplantation and identify potential markers.MethodsAllogeneic hindlimb transplantation were performed between Lewis (recipient) and Fischer344 (donor) rats with either constant immunosuppression or a high dose immunosuppressive bolus only in case of acute skin rejections. Histology, immunohistochemistry, microarray and qPCR analysis were used to detect changes in skin and muscle at postoperative day 100.ResultsWe were able to demonstrate significant intimal proliferation, infiltration of CD68 and CD4 positive cells, up-regulation of inflammatory cytokines and initiation of muscular fibrosis in the chronic rejection group. Microarray analysis and subsequent qPCR identified CXC ligands 9-11 as potential markers of chronic rejection.ConclusionsThe Fischer344 to Lewis hindlimb transplantation model may represent a new option to study chronic rejection in vascularized composite allotransplantation in an experimental setting. CXC ligands 9-11 deserve further research to investigate their role as chronic rejection markers.
| S-EPMC7319338 | biostudies-literature
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5â halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of âepigenetic carrierâ that mediate intergenerational inheritance of acquired traits. Mature sperm small-RNA profiles between High-fat-diet (HFD) and Normal-diet (ND) males; Transcriptional profiles of 8-cell embryos and balstocysts that developed from zygotes that injected with sperm RNAs from HFD vs ND males. Transcriptional profiles and RRBS profiles of islets of F1 offsrping that generated from zygotes that injected with sperm RNAs from HFD vs ND males.
2015-12-31 | E-GEOD-75544 | biostudies-arrayexpress
Project description:Transcriptome Profiling in a Porcine Vascular Composite Allotransplantation Model
| PRJEB72004 | ENA
Project description:Acute allograft rejection is a leading cause for the failure of organ allotransplantation. Identifying the genes involved in the rejection process provides clues to study the mechanisms, and to provide specific gene targets for monitoring, predicting and preventing acute allograft rejection. Using a mice model of skin acute allograft rejection and SAGE method, we analyzed gene expression in the CD4+ T cells of the mice, the cell type known to play critical roles in acute allograft rejection. Our study identifies 402 SAGE tags significantly different from these from the control. From these SAGE tags, we identified 91 increasingly and 85 decreasingly expressed genes, and many genes have not been linked with acute allograft rejection before. Functional classification of these genes shows that apoptosis, transcription regulation, cell growth and maintenance and signal transduction are among the most frequently changed functional groups. Our study provides a genome-wide view for the genes involving acute allograft rejection in the CD4+ T cells, and indicates that acute allograft rejection involves multiple genes in different functional categories. The genes identified from the study provide candidates for further studying the mechanisms and for monitoring, predicting and preventing acute allograft rejection.
2010-03-01 | GSE14540 | GEO
Project description:BackgroundA deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens.MethodsTwenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling.ResultsBiopsies with clinical signs and symptoms of rejection, irrespective of histopathological grading, were significantly enriched for genes contributing to the adaptive immune response, innate immune response, and lymphocyte activation. Inflammation episodes exhibited significant fold change correlations between the face and hands, as well as across patients. Immune checkpoint genes were upregulated during periods of inflammation that necessitated treatment. A gene signature consisting of CCL5, CD8A, KLRK1, and IFNγ significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention.ConclusionsThe mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.
| S-EPMC11415116 | biostudies-literature
Project description:Illumina tRFs & tiRNAs-seq analysis was used to characterize the whole transcriptomes of acute rejection caused by vascularized composite allotransplantation (VCA). tRFs & tiRNAs-seq information for muscle samples with VCA was obtained and compared with similar information for same age- and sex-matched healthy control subjects. The expression of 16 tRFs and tiRNAs, including 5 up-regulated target genes and 11 down-regulated target genes, were significantly different. According to bioinformatics analysis and reverse transcription quantitative polymerase chain reaction, we speculate that tiRNA-1-34-Glu-CTC-1 plays an important role in VCA-induced acute rejection by regulating the CACNA1D gene in the MAPK signaling pathway The findings provide the whole-transcriptome signatures of acute rejection for VCA, allowing further exploration of gene expression patterns/signatures associated with the various clinical symptoms of acute rejection for VCA.
| S-EPMC9452673 | biostudies-literature