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.
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).
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.
Project description:Mapping dynamic protein phosphorylation within trace samples deciphers cellular heterogeneity in signaling events and network activations for better understanding biology and disease mechanisms. We present a Chip-DIA strategy combining a microfluidic chip and data-independent acquisition mass spectrometry (DIA-MS) for sensitive nanoscale-to-single cell phosphoproteomic profiling.
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.
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.
Project description:Complex blood transcriptomes can lead to the clinical heterogeneity of systemic lupus erythematosus (SLE). In the current study, we integrated transcriptomics, public data mining and clinical parameters to reveal whether SLE severity is affected by specific genes or pathways.