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Project description:Background. Acute T cell-mediated rejection (ATMR) is a significant challenge in kidney allograft. Despite this, high-resolution transcriptomic analysis of both the targeted tissue and systemic blood is lacking. To address this void, we embarked on a study employing single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs), coupled with spatial transcriptomics analysis on graft biopsy specimens, to unveil the intricacies of ATMR. Methods. We collected paired pre- and post-operative blood samples from six kidney transplant patients. Among these, two patients exhibited a lack of rejection, while four patients bore biopsy-proven ATMR. By scrutinizing tissue samples from protocol biopsies taken two weeks post-operation in comparison to zero-time biopsies. Moreover, our investigation delved into peripheral blood samples, where we detected an expanded cell population within PBMCs, presumed to harbor numerous alloreactive T cells. This CD8+ effector memory (CD8 Tem) cell population was subsequently examined for DEGs between the two patient groups. Results. Our comprehensive approach, which combined scRNA-seq and spatial transcriptomics results, unveiled specific genes such as LTB, GZMK, STAT1, PSME2, UBE2L6, and GBP5, which showcased heightened expression levels among ATMR patients. Network analysis underscored the interconnection of STAT1 with the other identified genes, suggesting its plausible role in the rejection process. Conclusions. Our findings demonstrate CD8+ STAT1+ hold notable significance in the context of ATMR. This subpopulation undergoes clonal expansion and retains a memory phenotype, there by contributing to a heightened and swifter inflammatory response within the graft.
2023-12-03 | GSE248787 | GEO
Project description:Background. Acute T cell-mediated rejection (ATMR) is a significant challenge in kidney allograft. Despite this, high-resolution transcriptomic analysis of both the targeted tissue and systemic blood is lacking. To address this void, we embarked on a study employing single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs), coupled with spatial transcriptomics analysis on graft biopsy specimens, to unveil the intricacies of ATMR. Methods. We collected paired pre- and post-operative blood samples from six kidney transplant patients. Among these, two patients exhibited a lack of rejection, while four patients bore biopsy-proven ATMR. By scrutinizing tissue samples from protocol biopsies taken two weeks post-operation in comparison to zero-time biopsies. Moreover, our investigation delved into peripheral blood samples, where we detected an expanded cell population within PBMCs, presumed to harbor numerous alloreactive T cells. This CD8+ effector memory (CD8 Tem) cell population was subsequently examined for DEGs between the two patient groups. Results. Our comprehensive approach, which combined scRNA-seq and spatial transcriptomics results, unveiled specific genes such as LTB, GZMK, STAT1, PSME2, UBE2L6, and GBP5, which showcased heightened expression levels among ATMR patients. Network analysis underscored the interconnection of STAT1 with the other identified genes, suggesting its plausible role in the rejection process. Conclusions. Our findings demonstrate CD8+ STAT1+ hold notable significance in the context of ATMR. This subpopulation undergoes clonal expansion and retains a memory phenotype, there by contributing to a heightened and swifter inflammatory response within the graft.
2023-12-03 | GSE248788 | GEO
Project description:Discovering Molecular Signatures in ATMR: Single-cell RNA Sequencing Analysis of Human Blood and Tissue Spatial Transcriptomics [Spatial Transcriptomics]
| PRJNA1046018 | ENA
Project description:Discovering Molecular Signatures in ATMR: Single-cell RNA Sequencing Analysis of Human Blood and Tissue Spatial Transcriptomics
| PRJNA1046014 | ENA
Project description:Discovering Molecular Signatures in ATMR: Single-cell RNA Sequencing Analysis of Human Blood and Tissue Spatial Transcriptomics [scRNA-seq]
| PRJNA1046019 | ENA
Project description:Recent investigations of cell type changes in Multiple Sclerosis (MS) using single-cell profiling methods have focused on active lesional and peri-lesional brain tissue, and have implicated a number of peripheral and central nervous system cell types. However, an important question is the extent to which so-called "normal-appearing" non-lesional tissue in individuals with MS accumulate changes over the lifespan. Here, we compared post-mortem non-lesional brain tissue from donors with a pathological or clinical diagnosis of MS from the Religious Orders Study or Rush Memory and Aging Project (ROSMAP) cohorts to age- and sex-matched brains from persons without MS (controls). We profiled three brain regions using single-nucleus RNA-seq: dorsolateral prefrontal cortex (DLPFC), normal appearing white matter (NAWM) and the pulvinar in thalamus (PULV), from 15 control individuals, 8 individuals with MS, and 5 individuals with other detrimental pathologies accompanied by demyelination, resulting in a total of 78 samples. We identified region- and cell type-specific differences in non-lesional samples from individuals diagnosed with MS and/or exhibiting secondary demyelination with other neurological conditions, as compared to control donors. These differences included lower proportions of oligodendrocytes with expression of myelination related genes MOBP, MBP, PLP1, as well as higher proportions of CRYAB+ oligodendrocytes in all three brain regions. Among microglial signatures, we identified subgroups that were higher in both demyelination (TMEM163+/ERC2+), as well as those that were specifically higher in MS donors (HIF1A+/SPP1+) and specifically in donors with secondary demyelination (SOCS6+/MYO1E+), in both white and grey matter. To validate our findings, we generated Visium spatial transcriptomics data on matched tissue from 13 donors, and recapitulated our observations of gene expression differences in oligodendrocytes and microglia. Finally, we show that some of the differences observed between control and MS donors in NAWM mirror those previously reported between control WM and active lesions in MS donors. Overall, our investigation sheds additional light on cell type- and disease-specific differences present even in non-lesional white and grey matter tissue, highlighting widespread cellular signatures that may be associated with downstream pathological changes.
| S-EPMC10769298 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-03-28 | GSE293001 | GEO
Project description:Nociceptors are specialized sensory neurons that detect damaging or potentially damaging stimuli and are found in the dorsal root ganglia (DRG) and trigeminal ganglia. These neurons are critical for the generation of neuronal signals that ultimately create the perception of pain. Nociceptors are also primary targets for treating acute and chronic pain. Single-cell transcriptomics on mouse nociceptors has transformed our understanding of pain mechanisms. We sought to generate equivalent information for human nociceptors with the goal of identifying transcriptomic signatures of nociceptors, identifying species differences and potential drug targets. We used spatial transcriptomics to molecularly characterize transcriptomes of single DRG neurons from eight organ donors. We identified 12 clusters of human sensory neurons, 5 of which are C nociceptors, as well as 1 C low-threshold mechanoreceptors (LTMRs), 1 Aβ nociceptor, 2 Aδ, 2 Aβ, and 1 proprioceptor subtypes. By focusing on expression profiles for ion channels, G protein-coupled receptors (GPCRs), and other pharmacological targets, we provided a rich map of potential drug targets in the human DRG with direct comparison to mouse sensory neuron transcriptomes. We also compared human DRG neuronal subtypes to nonhuman primates showing conserved patterns of gene expression among many cell types but divergence among specific nociceptor subsets. Last, we identified sex differences in human DRG subpopulation transcriptomes, including a marked increase in calcitonin-related polypeptide alpha (CALCA) expression in female pruritogen receptor-enriched nociceptors. This comprehensive spatial characterization of human nociceptors might open the door to development of better treatments for acute and chronic pain disorders.
| S-EPMC9272153 | biostudies-literature
Project description:BackgroundThe tumor microenvironment (TME) serves as an important factor in tumorigenesis and metastasis. Although distinct cell subsets can be identified via single-cell RNA sequencing (scRNA-seq), the spatial composition of cells within the TME is difficult to characterise.MethodsTissue samples were collected from three patients with esophageal squamous cell carcinoma (ESCC), and scRNA-seq was performed to identify distinct cell subsets. In addition, a microarray-based spatial transcriptomics (ST) method was used to characterise the spatial landscape of expression data via an array of spots. Using multimodal intersection analysis (MIA) to integrate scRNA-seq and ST, the exact cellular components of the tumor and stromal regions were annotated.FindingsThe subpopulations of seven stromal cells were identified within the TME of ESCC, and the architecture of scRNA-seq-determined subsets was mapped in cancer and stromal regions. The distribution of various stromal cells and their subpopulations was heterogeneous. Compared with immune cells, non-immune stromal cells were significantly enriched in the TME. Most subsets of epithelial cells were enriched in the cancer regions, whereas inflammatory cancer-associated fibroblasts were correlated with the stromal regions. Furthermore, TME features were different between metastatic and non-metastatic samples and between the primary and metastatic sites of the metastatic sample.InterpretationThis study revealed the spatial landscape of various cell subsets within the TME and the potential cross-talk among diverse cells, which provides novel insights into cancer intervention.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
| S-EPMC9519476 | biostudies-literature
Project description:Bladder Ewing sarcoma/primitive neuroectodermal tumor (bladder ES/PNET) is a rare and highly malignant tumor associated with a poor prognosis, yet its underlying mechanisms remain poorly understood. Here, we employed a combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and functional analyses to delve into the pathogenesis of bladder ES/PNET. The investigation revealed the presence of specialized types of epithelial cells (referred to as bladder ES-Epi) and mast cells (referred to as bladder ES-Mast) within bladder ES/PNET in comparison to urothelial carcinoma. Notably, TNFRSF12A exhibited significant upregulation in bladder ES/PNET. Furthermore, mast cells possessed the ability to activate epithelial cells through the TNFSF12-TNFRSF12A ligand-receptor signaling pattern. In addition, Enavatuzumab can significantly inhibit the migratory ability of the Ewing sarcoma cell line RD-ES. This groundbreaking study provides unprecedented mechanistic insights into the progression of bladder ES/PNET and introduces a potential therapeutic avenue for treating this challenging malignancy.
| S-EPMC11462044 | biostudies-literature