Mapping SLE heterogeneity at the single cell level
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ABSTRACT:
PROVIDER: PRJNA640197 | ENA |
REPOSITORIES: ENA
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Project description:Mapping SLE heterogeneity at the single cell level
| PRJNA640196 | ENA
Project description:Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays a significant gender difference in terms of incidence and severity. However, the underlying mechanisms accounting for sexual dimorphism remain unclear. To reveal the heterogeneity in the pathogenesis of SLE between male and female patients. PBMC were collected from 15 patients with SLE (7 males, 8 females) and 15 age-matched healthy controls (7 males, 8 females) for proteomic analysis. Enrichment analysis of proteomic data revealed that type I interferon signaling and neutrophil activation networks mapped to both male and female SLE, while male SLE has a higher level of neutrophil activation compared with female SLE. Our findings define gender heterogeneity in the pathogenesis of SLE and may facilitate the development of gender-specific treatments.
2022-08-12 | PXD033144 | Pride
Project description:In this study, we analyzed the transcriptomes of ~276k single PBMCs from 33 childhood SLE (cSLE) and 11 healthy matched donors (cHD). Our findings were validated in an independent cohort including 8 adult SLE (aSLE) patients and 6 matched controls (aHD; ~132k PBMCs).
2020-09-02 | GSE135779 | GEO
Project description:Lupus, a server and complex autoimmune disease, is clinically divided into cutaneous lupus erythematosus (CLE) which featured in skin damage, and systemic lupus erythematosus (SLE) which characterized in systemic multi-organ damage. The distinction of these two types of lupus is widely unknown. Here, we collected 23 skin biopsies of healthy control(HC), DLE (discoid lupus erythematosus, a main type of CLE) and SLE, separated epidermis and dermis and performed single cell RNA sequencing through microfluidics based 10x genomics system. Our results demonstrated larger numbers of immune cells infiltrated in skin lesions of DLE than SLE, which may help to distinguish them. Then, non-immune cells such as keratinocytes and fibroblasts were showed functions like immune cells. Moreover, ISGs(interferon stimulated genes), HSP70 coding genes were found to be overexpressed in multi expanded subclusters. Some biological progresses such as autophagy and neutrophil activation were enriched in expanded subclusters.
2022-10-17 | GSE179633 | GEO
Project description:Systemic lupus erythematosus (SLE) affects 1 in 537 of African American (AA) women, which is >2-fold more than European American (EA) women. AA patients also develop the disease at a younger age, have more severe symptoms, and a greater chance of early mortality. We used a multi-omics approach to uncover ancestry-specific immune alterations in SLE patients and healthy controls that may contribute to disease disparities. Cell composition, signaling, and epigenetics were evaluated by mass cytometry; droplet-based single cell transcriptomics and paired proteogenomics (scRNA-Seq/scCITE-Seq). Soluble mediator levels were measured in plasma and stimulated whole blood. TLR3/4/7/8/9 gene expression pathways in B cells and monocytes were enhanced in AA SLE patients compared to EA patients. TLR7/8/9 and IFN phospho-signaling responses were also heightened in healthy AA versus EA controls. Exposure of AA and EA healthy control cells to TLR7/8/9 agonists or IFN resulted in altered immune cell compositions that recapitulated the ancestry-associated differences in SLE patients. These data support that ancestry-based differences in TLR7/8, TLR9, and IFN responses that can be detected in healthy individuals could influence lupus disease course and severity.
2023-10-11 | GSE189050 | GEO
Project description:We combined the Single-probe single cell MS(SCMS) experimental technique with a bioinformatics software package, SinCHet-MS (Single Cell Heterogeneity for Mass Spectrometry), to characterize changes of tumor heterogeneity, quantify cell subpopulations, and prioritize the metabolite biomarkers of each subpopulation.
2023-06-15 | MSV000092178 | GNPS
Project description:A single cell approach to map cellular subsets involved in Systemic Lupus Erythematosus (SLE) heterogeneity
| PRJNA560047 | ENA
Project description:Single-nucleotide–level mapping of DNA regulatory elements that control fetal hemoglobin expression
| PRJNA660803 | ENA
Project description:Glioblastoma (GBM) is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance, recurrence and progression. While regional and single cell transcriptomic variations of GBM have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned to specific niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to GBM’s hallmark histomorphologic niches across 20 patients and define distinct molecular programs operational within these regional tumor compartments. Using machine learning, we overlay concordant transcriptional information, and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. Importantly, we show using multiple cohorts, that GBMs with an enhanced KRAS component harbor a more clinically aggressive and infiltrative phenotype. Conversely, tumor cells enriched along the MYC axis where mutually exclusive and had a distinct proliferative program. Moreover, by applying both experimental and computational approaches to link each of these distinct molecular axes with potential pharmacological therapies, we highlight differential drug sensitivities and a notable relative chemoresistance in GBM cell lines with enhanced KRAS programs. Importantly, pharmacological differences were less evident when using traditional expression-based subgroups supporting thattopographic phenotypic mapping ofGBM, and the proposed axes may provide new insights for targeting heterogeneity and overcoming therapy resistance in this aggressive disease.
2021-11-02 | PXD029290 | Pride
Project description:Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by pathogenic auto-antibodies that cause end organ damage. B cells are thought to play a central role in the immunopathogenesis of SLE and display several abnormalities in patients, including a strong type I interferon signature as well as lower expression of surface markers including TLR9 and FcγRIIB. To characterize differences in the proportion of distinct B cell subsets as well as intrinsic transcriptomic differences between B cells from healthy donors and SLE patients, we performed single-cell RNA sequencing on B cells isolated from PBMCs of donors. Several notable features were observed, including a strong interferon response signature among SLE B cells, and the expansion of CD11c+T-bet+ B cell subsets in these patients. Additionally, several surface molecules including MHC Class II proteins and surface proteins such as CD74 and CD52 were found to be differentially expressed in B cells isolated from SLE patients. The differences in B cell subset proportion as well as expression of various genes might play a role in B cell mediated pathogenesis of SLE.
2020-12-14 | GSE163121 | GEO