Clonal expansion of T regulatory cells in rejecting versus tolerant mouse lung grafts
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE251965 | GEO | 2025/02/28
REPOSITORIES: GEO
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Project description:Clonal expansion of T regulatory cells in rejecting versus tolerant mouse lung grafts
| PRJNA1056046 | ENA
Project description:To gain insights into the genetic program activated within the distinct vascular and inflammatory transplant microenvironments in Id1/Id3 deficient and WT mice, we performed a series of gene screening experiments using RNA from total graft tissue as well as from myeloid and endothelial (i.e., CD31+ and ISB4+) cells isolated from the grafts at 1 week post-transplantation.
2008-06-13 | E-TABM-355 | biostudies-arrayexpress
Project description:anti-CD4, CD8 and CD40L treated versus control murine CD4+ T cells from micegrafted with hESC derived xenografts. Human embryonic stem cells (ESCs), by virtue of their capability to self-renew and differentiate into almost all body cell types, represent the first type of pluripotent stem cells (PSCs) to be used in clinical transplantation to humans in recent phase-I trials. As it is unlikely that any such cells or their progeny will survive in an allogeneic host, there is an urgent need to understand how to get long-term acceptance and functional differentiation with minimal immunosuppression. Here, we show that brief induction with combined monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term survival and engraftment of murine ESCs, human ESCs, human induced PSCs, and human ESC-derived progenitor cells from all three embryonic germ layers. Tolerance induced to PSC-derived progenitors appears, remarkably, to extend to protection of their differentiated progenies, and sometimes even to different tissues derived from the same donor, suggesting linked-suppression as a likely operative mechanism. These results suggest that once tolerance has been established to PSC-derived progenitor cells, it can be extended to their differentiated progenies. Global gene expression profiling of graft infiltrating T-lymphocytes identifies gene sets that differ between rejecting and tolerant populations including gene upregulation in pathways associated with apoptosis, cell adhesion, transcription suppression and TGF synthesis; and gene downregulation in pathways associated with inflammation in recipients treated with combined coreceptor and costimulation blockade. Mice grafted with hESC derived tissues and untreated (control) or tolerised via injections of anti-CD4, anti CD8 and CD40L. CD3+ T cells isolated from the gratfs 30 days later.
2014-09-30 | E-GEOD-61867 | biostudies-arrayexpress
Project description:anti-CD4, CD8 and CD40L treated versus control murine CD4+ T cells from micegrafted with hESC derived xenografts. Human embryonic stem cells (ESCs), by virtue of their capability to self-renew and differentiate into almost all body cell types, represent the first type of pluripotent stem cells (PSCs) to be used in clinical transplantation to humans in recent phase-I trials. As it is unlikely that any such cells or their progeny will survive in an allogeneic host, there is an urgent need to understand how to get long-term acceptance and functional differentiation with minimal immunosuppression. Here, we show that brief induction with combined monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term survival and engraftment of murine ESCs, human ESCs, human induced PSCs, and human ESC-derived progenitor cells from all three embryonic germ layers. Tolerance induced to PSC-derived progenitors appears, remarkably, to extend to protection of their differentiated progenies, and sometimes even to different tissues derived from the same donor, suggesting linked-suppression as a likely operative mechanism. These results suggest that once tolerance has been established to PSC-derived progenitor cells, it can be extended to their differentiated progenies. Global gene expression profiling of graft infiltrating T-lymphocytes identifies gene sets that differ between rejecting and tolerant populations including gene upregulation in pathways associated with apoptosis, cell adhesion, transcription suppression and TGF synthesis; and gene downregulation in pathways associated with inflammation in recipients treated with combined coreceptor and costimulation blockade.
2014-09-30 | GSE61867 | GEO
Project description:Dopaminergic neurons (DAn), generated from human pluripotent stem cells (hPSC), are capable of functionally integrating following transplantation and have recently advanced to clinical trials for Parkinson’s disease (PD). However, pre-clinical studies have highlighted the low proportion of DAn within hPSC-derived grafts and their inferior plasticity compared to fetal tissue. Here we examined whether delivery of a developmentally critical protein, glial cell line-derived neurotrophic factor (GDNF), could improve graft outcomes. We tracked the response of DAn implanted into either a GDNF-rich environment, or after a delay in exposure. Early GDNF promoted survival and plasticity of non-DAn, leading to enhanced motor recovery in PD rats. Delayed exposure to GDNF promoted functional recovery through increases in DAn specification, DAn plasticity and dopamine metabolism. Transcriptional profiling revealed a role for MAPK-signalling downstream of GDNF. Collectively these results demonstrate the potential of neurotrophic gene therapy strategies to improve hPSC graft outcomes.
2020-01-06 | GSE143136 | GEO
Project description:Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p<0.005). Many up-regulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of down-regulated genes were linked to hepatic metabolism and energy pathways correlating with post-transplant clinical laboratory findings. There was significant up-regulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant down-regulation of metabolic pathways in LD grafts. Keywords: liver transplantation, live donor transplantation, liver regeneration, microarrays, mRNA expression, reperfusion injury
2009-06-11 | GSE12720 | GEO
Project description:We performed a transcriptome analysis on the graft junction of tomato and pepper self grafts and heterografts.
2021-09-30 | GSE167482 | GEO
Project description:IPSC-NPC were transplanted in a mouse model of stroke. To dissect the molecular graft composition and identify graft-host interactions, single nucleus profiling of the cell transplants and host stroke tissue was performed. We identified graft differentiation preferentially towards GABAergic cells with remaining cells acquiring glutamatergic neuron, astrocyte, and NPC-like phenotypes. Interaction between graft and host transcriptome indicated that GABAergic cell grafts were primarily involved in graft-host communication through the regeneration-associated NRXN, NRG, NCAM and SLIT signalling pathways
2025-08-06 | GSE259430 | GEO
Project description:Acute rejection remains an important risk factor affecting the survival of recipients following transplantation. Bone marrow mesenchymal stem cells (BMMSCs) are used in the treatment of organ transplantation due to their immunomodulatory ability. BMMSCs were isolated from rat bone marrow and modified with the adenovirus for heme oxygenase 1 (HO-1) gene. Saline solution, BMMSCs or HO-1/BMMSCs were perfused into the donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by liver transplantation. The liver grafts were collected at 7 days post-transplantation. Gene chip technology was used to detect differential gene expression.
2021-03-02 | GSE167980 | GEO
Project description:Understanding wound healing in vaginal tissue is crucial for improving female health outcomes, particularly in the context of surgeries like pelvic organ prolapse, post-radiation stricture formation and complications resulting from vaginal childbirth. Tissue-engineered grafts have proven successful for vaginal tissue repair, however, the mechanisms that stimulate tissue repair are unknown. This study aims to explore the transcriptomic signatures during tissue repair after using autologous micrografting versus acellular grafts in a rabbit model for surgical vaginal reconstruction. During a single surgical procedure, we created a graft for vaginal reconstruction consisting of autologous micrografts and supporting biomaterials. This graft was named "perioperative, layered, autologous, tissue expansion (PLATE)." We also produced acellular grafts that lacked autologous micrografts,. Our findings revealed distinct differences in gene expression patterns associated with wound healing, extracellular matrix organization, and smooth muscle regeneration between the two graft types. Notably, our findings revealed that micrografting showed an accelerated progression towards the final stages of wound healing, as evidenced by elevated matrix metalloproteinase (MMP) expression, particularly MMP-13. Additionally, Transforming Growth Factor Beta-1 (TGF-β1) emerged as an expected vaginal wound healing regulator. This study provides valuable insights into the molecular mechanisms of PLATE grafts and opens new avenues for the development of targeted therapies to improve wound healing in vaginal tissues.
2025-02-10 | GSE252016 | GEO