Project description:To explore the cellullar and molecular alteration of human psoriasis, we collected full-thickness skin from the lesion region of 3 patients and the similar region of 3 healthy donors, and submit for single cell RNA sequencing (scRNAseq) with 10x genomics (V3.1). The transcriptional landscape of human psoriasis whole skin provide a unique view of immuno-regulation among skin cell types. 1. "Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis",<Cell Death Dis.>, 2021 May 6;12(5):450. https://yz-studio.shinyapps.io/shinyapph5ad/ 2. "Integrative single-cell transcriptomic investigation unveils long non-coding RNAs associated with localized cellular inflammation in psoriasis" <Front Immunol>2023 Sep 26:14:1265517. Integrated dataset: 106,675 cells from 11 healthy human skin and 79,887 cells from 9 psoriatic human skin https://yz-studio.shinyapps.io/psoriaticskincellatlas2/
Project description:Background: Based on the mounting evidence that Type 17 T-cells (T17 cells) and increased IL-17 play a key role in driving hidradenitis suppurativa (HS) lesion development, biologics previously used in psoriasis that block signaling of IL-17A and/or IL-17F isoforms have been repurposed to treat HS. Objective: Our aim was to characterize the transcriptome of HS T17 cells compared to the transcriptome of psoriasis T17 cells, and their ligand-receptor interactions with neighborhood immune cell subsets. Methods: Single-cell data of 12,300 cutaneous immune cells from 8 de-roofing surgical HS skin samples that included dermal tunnels were compared with single-cell data of psoriasis skin (19,525 cells from 11 samples) and control skin (11,920 cells from 10 samples). All the single-cell data were generated by the identical protocol. Results: HS T17 cells expressed lower levels of IL23R and higher levels of IL1R1 and IL17F compared to psoriasis T17 cells (p < 0.05). HS regulatory T-cells (Tregs) expressed higher levels of IL1R1 and IL17F compared to psoriasis Tregs (p < 0.05). Semimature dendritic cells (DCs) were the major immune cell subsets expressing IL1B in HS, and IL-1B ligand-receptor interactions between semimature DCs and T17 cells were increased in HS compared to psoriasis (p < 0.05). HS dermal tunnel keratinocytes (KCs) expressed inflammatory cytokines (IL17C, IL1A, IL1B, and IL6) different from HS epidermis KCs (IL36G) (p < 0.05). IL6, which synergizes with IL1B to maintain cytokine expression in T17 cells, was mainly expressed by fibroblasts in HS, which also expressed IL11+ inflammatory fibroblast genes (IL11, IL24, IL6, and POSTN) involved in paracrine IL-1/IL-6 loop. Conclusion: The IL-1B-T17 cell cytokine axis is likely a dominant pathway in HS with HS T17 cells activated by IL-1B signaling, unlike psoriasis T17 cells which are activated by IL-23 signaling. Clinical Implication: Biologics targeting IL-17 isoforms and IL-1B may be effective for HS but biologics targeting IL-23 may be less effective for HS.
Project description:Bilateral renal cell carcinoma (RCC) is a rare type of this disease and includes familial bilateral and sporadic bilateral RCCs. Studying the cellular molecular characteristics of sporadic bilateral is important to provide a direct guide for clinical treatment. These cellular molecular characteristics can be expressed at the RNA level, especially at the single-cell RNA level. Single-cell RNA sequencing (scRNA-seq) was performed on bilateral clear cell RCC (ccRCC). A total of 3,575 and 3,568 high-quality single-cell transcriptome data were captured from the left and right tumour tissues, respectively. Gene characteristics were identified by comparing left and right tumours at the scRNA level. This work presented the complex cellular environment of bilateral ccRCC by scRNA-seq. Single-cell transcriptome analysis revealed high similarity in gene expression among most cell types of bilateral RCCs but significant differences in gene expression among different site tumour cells. Additionally, the potential biological function of different tumour cell types was determined by gene ontology (GO) analysis. The transcriptome characteristics of tumour tissues in different locations at the single-cell transcriptome level were revealed through the scRNA-seq of bilateral sporadic ccRCC. This work provides new insights into the diagnosis and treatment of bilateral RCC.
Project description:The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is still incompletely understood. Here we demonstrate, using a combination of single-cell and spatial-sequencing, that psoriatic fibroblasts, a hitherto unappreciated participant in psoriasis pathogenesis, contribute to the immune network in psoriasis through transition to a pro-inflammatory state characterized by CCL19 and CCL13. Fibroblasts interact with three other main cell-types that are in close proximity: keratinocytes, T cells and myeloid cells, that also interact with each other. In addition, our data demonstrates striking compartmentalization of inflammatory responses in distinct layers of the psoriatic epidermis, including IL-17A responses and autocrine IL-36 autoinflammatory activity within the supraspinous layer. Lastly, our data defined the T cell and myeloid populations involved in psoriasis, including enrichment of CD8+ IL17A expressing T cells, CD16+ dendritic cells, and LAMP3+ dendritic cells. These data provide an unprecedented view of psoriasis pathogenesis, which expands our understanding of the critical cellular players to include inflammatory fibroblasts as well as their cell-cell interactions, defines the spatial compartmentalization of specific inflammatory processes, together a unique resource for future investigations.
Project description:Skin biopsy from the previously resolved region (PN), the autologous on-site recurrence with psoriatic plaque (PP)and the non-lesion control (CN) were obtained from the lower back of four male plaque psoriasis patients. Single-cell RNA sequencing (scRNA-seq) was performed after cell dissociation. In our article, sub-clustering and characterization of T cells were demonstrated, functional comparisons of T-cell subsets were conducted further among PN, PP and CN.
Project description:The study focuses on the cellular composition of the psoriasis epidermis, using single-cell transcriptomics to identify cell subsets and their interactions in both healthy and psoriatic skin. The research uncovers three keratinocyte populations and seven immune cell subsets exclusive to psoriatic lesions. A significant finding is the identification of a previously undetected population of plasmacytoid dendritic cells (pDCs) in the psoriatic epidermis, suggesting their role in the disease's pathogenesis. The study also highlights enhanced keratinocyte-immune cell interactions in psoriatic lesions, contributing to our understanding of psoriasis at the cellular level.
Project description:Single-cell RNA sequencing is transforming how we understand skin immunology, but previous human skin single-cell RNA sequencing data included only a small fraction of inflammatory cells among the overall cell population, such that functional subsets may be difficult to ascertain. We have overcome these obstacles by harvesting inflammatory cells emigrating from a half of 6 mm punch biopsy skin after 48-hour incubation in culture medium without any enzyme, and then analyzing the harvested cells with single-cell RNA sequencing. By this strategy, we obtained single-cell RNA sequencing data of 24,354 cells (leukocytes 46.0%, keratinocytes 49.6%, and melanocytes 2.4%) from 13 human psoriasis skin and 5 healthy volunteer skin. Unsupervised clustering identified NK cells, CD161+ T-cells, CD8+ T-cells, CD4+ T-cells, regulatory T-cells, mature & semimature dendritic cells, melanocytes, and keratinocytes in different layers - S. (Stratum) corneum, S. granulosum, S. spinosum, and S. basale. To understand psoriasis immunopathogenesis at single-cell levels, we compared gene expression between psoriasis cells vs. control cells within each inflammatory cell subtype clusters.