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Single-cell multi-omic analysis of post-transplant mesenchymal cells reveals molecular signatures and regulators of lung fibrosis (RNA-seq)

ABSTRACT: Chronic lung allograft dysfunction (CLAD) is a critical challenge in lung transplantation. Dysregulated gene expression and epigenomic states in lung mesenchymal cells (MCs) play a key role in these conditions. We performed single-cell multi-omic profiling on MCs isolated from human bronchoalveolar lavage samples of lung transplant recipients with CLAD, compared with time-matched controls. Our results provide deeper insights into the transcriptomic and epigenomic changes in post-transplant MCs, nominating biomarkers and disease-associated factors with implications for future therapeutic efforts.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281481 | GEO | 2026/03/29

REPOSITORIES: GEO

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Single-cell multi-omic analysis of post-transplant mesenchymal cells reveals molecular signatures and regulators of lung fibrosis (scRNA-seq)

Project description:Chronic lung allograft dysfunction (CLAD) is a critical challenge in lung transplantation. Dysregulated gene expression and epigenomic states in lung mesenchymal cells (MCs) play a key role in these conditions. We performed single-cell multi-omic profiling on MCs isolated from human bronchoalveolar lavage samples of lung transplant recipients with CLAD, compared with time-matched controls. Our results provide deeper insights into the transcriptomic and epigenomic changes in post-transplant MCs, nominating biomarkers and disease-associated factors with implications for future therapeutic efforts.

2026-03-29 | GSE282248 | GEO

Gene expression profiling of bronchoalveolar lavage cells preceding a clinical diagnosis of chronic lung allograft dysfunction

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

Gene expression profiling of bronchoalveolar lavage cells during Aspergillus colonization of the lung allograft

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

Single cell and spatial transcriptomic profile of whole CLAD and donor control lung tissue

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

NKG2D blockade impairs cytotoxic CD8+ tissue resident memory T cell accumulation and attenuates severity of chronic lung allograft dysfunction after transplantation

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

RNA-seq of bronchoalveolar lavage samples of lung transplant primary graft dysfunction

Project description:This is an RNA-seq study of human lung transplant recipients. Bronchoalveolar lavage cells were collected on the first day after lung transplant. We performed bulk RNA-sequencing on 19 lung transplant recipients with severe primary graft dysfunction (PGD) and 19 lung transplant recipients without primary graft dysfunction. As this data is human identifiable, raw data are not included in this record.

2023-02-15 | E-MTAB-12282 | biostudies-arrayexpress

Human Lung Transplant - BAL

Project description:Bronchoalveolar lavage samples collected from lung transplant recipients. Numeric portion of sample name is an arbitrary patient ID and AxBx number indicates the perivascular (A) and bronchiolar (B) scores from biopsies collected on the same day as the BAL fluid was collected. Several patients have more than one sample in this series and can be determined by patient number followed by a lower case letter. Acute rejection state is determined by the combined A and B score - specifically, a combined AB score of 2 or greater is considered an acute rejection. Keywords = Bronchoalveolar lavage Keywords = lung transplant Keywords: other

2004-11-30 | GSE2018 | GEO

Lung transplant

Project description:Lung transplant

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singlecell RNA sequencing of lung transplanted mice

Project description:This dataset contains single-cell RNA sequencing (scRNA-seq) data from murine lung transplantation models. The study investigates the expression of fibroblast activation protein (FAP) as an early biomarker in chronic lung allograft dysfunction (CLAD). Lung samples were collected at baseline, day 7, and day 28 post-transplantation to analyze gene expression patterns associated with fibrotic remodeling. This dataset provides insights into the cellular heterogeneity and dynamic changes occurring in lung allografts during CLAD progression.

2026-02-02 | GSE289883 | GEO

Whole blood gene expression from lung transplanted patients with chronic lung allograft dysfunction

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

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