Singlecell RNA sequencing of lung transplanted mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE289883 | GEO | 2026/02/02
REPOSITORIES: GEO
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Project description:Chronic lung allograft dysfunction (CLAD) limits the long term survival after lung transplantation. CLAD is diagnosed late on the decline in lung function, when any immuno-intervention is ineffective. Identification of early forerunners of CLAD is therefore essential to prevent the progression of the disease before irreversible damages to the allograft. We used large-scale gene expression profiling of whole blood cells to identify early biomarkers of Bronchiolitis Obliterans Syndrome (BOS), the main form of CLAD. Microarray experiments performed from 80 patients (40 stable (STA) and 40 BOS) identify 47 genes differentially expressed between STA and BOS recipients. An independent set of patients (13 STA, 11 BOS) was then used for external validation by qPCR. POU Class 2 Associating Factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A) and B-cell lymphocyte kinase (BLK) genes were identified and validated as predictive markers of BOS more than 6 months before diagnosis with AUCs of 0.83, 0.77 and 0.78 respectively. These genes allow stratifying upon CLAD risk (log-rank test p<0.01) and could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.
2018-02-23 | GSE94557 | GEO
Project description:Transcriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on day 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-ï§-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection. Endothelial cells were enriched from control/non-transplanted hearts and from allografts (DA to Lewis) and isografts (Lewis to Lewis) harvested at day 2, 3 and 4 after transplantation. Three biological replicates from each time point and graft type were analyzed (a total of 24 arrays). Leukocytes were enriched from allografts at day 2 (n=1), day 3 (n=2) and day 4 (n=1) after transplantation.
2010-07-29 | E-GEOD-16695 | biostudies-arrayexpress
Project description:Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects. In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n=9) and CLAD free (n=8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis was performed to identify a candidate list of differentially expressed probe sets.
2017-01-04 | E-MTAB-5029 | biostudies-arrayexpress
Project description:Chronic lung allograft dysfunction (CLAD) significantly limits long-term survival following lung transplantation. To identify potential targets for CLAD prevention, T cells from explanted CLAD lungs and lung-draining lymph nodes, as well as diseased and non-diseased controls were isolated and single-cell RNA sequencing and TCR sequencing were performed. TCR sequencing revealed a clonally expanded population of tissue resident memory (TRM) CD8+ T cells with high cytotoxic potential including upregulation KLRK1, encoding the co-receptor NKG2D. These cytotoxic CD8+ TRM accumulated around the CLAD airways and had 100-fold increase in clonal overlap with lung draining lymph nodes when compared to non-CLAD lungs. Using a murine model of orthotopic lung transplant, we confirmed that cytotoxic CD8+ TRM accumulation was due to chronic rejection and not transplant alone. Furthermore, blocking NKG2D in-vivo attenuated the airway remodeling following transplantation and diminished airway accumulation of CD8+ T cells. Our findings support NKG2D as a potential therapeutic target for CLAD, affecting cytotoxic CD8+ TRM accumulation.
2024-12-29 | GSE285515 | GEO
Project description:Background: Bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction (CLAD), is the major limitation to long-term survival after lung transplantation. The patho-anatomical correlate is progressive, fibrotic occlusion of the small airways, so-called obliterative bronchiolitis (OB) –lesions, ultimately leading to organ failure. The molecular composition of these lesions is unknown. Methods: By combining laser-capture microdissection (LCM) and optimized sample preparation protocols for mass spectrometry (MS) we analyzed end-stage OB-lesions identified in explanted lungs from four end-stage BOS patients. Immunohistochemistry and immunofluorescence were used to follow selected proteins of interest on the tissue level. Results: We established protein signatures for in total 15 OB-lesions. A set of 12 proteins identified in all lesions included both distinct structural proteins (collagen type IV and VI) and cellular components (actins, vimentin, tryptase). Each respective lesion exhibited a unique composition of proteins (on average n=66), thereby mirroring the histomorphological variation of the lesions. Conclusions: Even though being distinct and focal pathologic events, OB-lesions showed considerable variations in their protein content, most likely reflecting different disease pathways. Combining spatial information and advanced protein identification, this study provides molecular and morphological insights essential for a better understanding of the development of chronic rejection after lung transplantation.
2021-05-19 | PXD014171 | Pride
Project description:Transcriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on day 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-gamma-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection.
2010-07-06 | GSE16695 | GEO
Project description:Chronic lung allograft dysfunction (CLAD) is the leading cause of death in lung transplant recipients. CLAD is characterized clinically by a persistent decline in pulmonary function and histologically by the development of airway centered fibrosis known as bronchiolitis obliterans. We performed single-cell sequencing and spatial transcriptomic analysis of explanted tissues from human lung recipients with CLAD and donor control lungs.
2023-03-21 | GSE224210 | GEO
Project description:Background: Aspergillus colonization after lung transplant is associated with an increased risk of chronic lung allograft dysfunction (CLAD). We hypothesized that gene expression during Aspergillus colonization could provide clues to CLAD pathogenesis. Methods: We examined transcriptional profiles in 3 or 6-month surveillance bronchoalveolar lavage fluid cell pellets from recipients with A. fumigatus colonization (n=12) and without colonization (n=10). Among the Aspergillus colonized, we also explored profiles in those who developed CLAD (n=6) or remained CLAD free (n=6). Transcription profiles were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Statistical Analysis: Differential gene expression analyses were performed to select candidate lists of genes. Functional analyses on these selected genes were explored.
2017-10-22 | E-MTAB-6040 | biostudies-arrayexpress
Project description:C57/BL6 to C57/BL6 Balb/c to C57/BL6 Balb/c to C57/BL6 with anti CD80/86 mAb Identificaton of gene expression profile in tolerizing murine cardiac allograft by co-stimulatory blockade. The induction of specific tolerance would be the ultimate achievement in transplant immunology, but the precise mechanisms of immunological tolerance remain largely unknown. Here, we investigated global gene expression analysis in tolerizing murine cardiac allografts by means of oligonucleotide microarrays. Tolerance induction was achieved in cardiac allografts from BALB/c to C57BL/6 mice by daily intraperitoneal injection of anti-CD80 and CD86 mAbs. Comparative analysis revealed 64 genes to be induced more extensively in the tolerizing than in the syngeneic isografts, and 16 genes than in the rejecting allografts. Two genes were specifically upregulated in the tolerizing allografts. In the tolerizing allografts there were induced marked expressions of a number of genes for proinflammatory factors, including interferon-gamma inducible cytokines and chemokines, as well as apoptosis-related genes which were also upregulated in the rejecting allografts. Moreover, these gene expression patterns continued to be upregulated more than 70 days post transplant. These results provide evidence that immunological tolerance can be induced and maintained in the presence of prominent proinflammatory gene expression in vivo. Keywords: other
2003-10-14 | GSE582 | GEO
Project description:Lymph node stromal cells (LNSCs) are the master regulator of the LN microenvironment. Single-cell genomics has revealed a multitude of LNSCs subsets, each playing unique and critical roles in immune responses and tissue homeostasis. However, the role of specific LNSC subsets controlling tolerance within draining LNs (DLNs) in heart allograft transplanted recipients remains to be explored. In order to assess the phenotype of LNSCs and effect of LNSCs on transplant tolerance or allograft rejection after heart transplantation, we performed single cell RNA sequencing (scRNA-seq) of LNSCs from naive mice and heart allograft transplanted mice with/without anti-CD40L (day8 after heart transplantation, anti-CD40L (250 μg, day 0)).
2025-04-02 | GSE262918 | GEO