The pathogenesis of psoriasis, a chronic inflammatory autoimmune skin disease with a high global prevalence, remains unclear. We performed a high-resolution single-cell RNA sequencing analysis of 94,759 cells from 13 samples, including those from psoriasis model mice and wild-type mice. We presented a single-cell atlas of the skin of imiquimod-induced mice with psoriasis and WT mice, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial–mesenchymal transition and validated the results with drug verification. Moreover, we conducted a tentative exploration of the potential pathways involved and revealed that the IL-17 signalling pathway may be the most relevant pathway. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

The functional performance of immune cells relies on a complex transcriptional regulatory network. The three-dimensional structure of chromatin can affect chromatin status and gene expression patterns, and plays an important regulatory role in gene transcription. Currently available techniques for studying chromatin spatial structure include chromatin conformation capture techniques and their derivatives, chromatin accessibility sequencing techniques, and others. Additionally, the recently emerged deep learning technology can be utilized as a tool to enhance the analysis of data. In this review, we elucidate the definition and significance of the three-dimensional chromatin structure, summarize the technologies available for studying it, and describe the research progress on the chromatin spatial structure of dendritic cells, macrophages, T cells, B cells, and neutrophils.

Chromatin accessibility plays a crucial role in mediating transcriptional dysregulation and heterogeneity in Esophageal Squamous Cell Carcinoma (ESCC). Examining the chromatin accessibility of ESCC at single-cell level is imperative to understand how it activates oncogenes and contributes to the onset and metastasis of ESCC. We performed single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on cancerous and adjacent noncancerous tissues from four ESCC patients who were pathological staged as T1a, T2b, T3b, or T4a, to investigate whether regulatory elements are pivotal in instigating cellular heterogeneity during ESCC metastasis. In conjunction, we integrated these data with 55 scRNA-seq datasets, ChIP-seq or CUT&Tag sequencing data, Hi-C sequencing data, bulk RNA-seq data, and bulk ATAC-seq data from ESCC cell lines to dissect the mechanisms underlying the heterogeneity of ESCC and tumor microenvironment (TME). Our study identified enhancer-specific activation within epithelial cells orchestrated by the three-dimensional structure of chromatin that regulates SERPINH1 transcription, and promotes the epithelial-mesenchymal transition (EMT) and metastasis of ESCC. Additionally, chromatin element activation facilitated the expression of TNFSF4 in CD8 + exhausted T cells, thereby activating Tregs. Furthermore, we observed that chromatin accessibility promoted the differentiation of tumor-associated macrophages (TAMs) and cancer associated fibroblasts (CAFs). In summary, utilizing multiomics analyses, we have revealed chromatin accessibility maps and illuminated the intricate molecular mechanisms that underlie cellular heterogeneity during ESCC metastasis, offering valuable insights to further advance research on tumor progression and deterioration.

As a chronic inflammatory autoimmune skin disease with high global prevalence, the pathogenesis of psoriasis remains inconclusive. We performed a high-resolution single-cell RNA sequencing analysis of 94 759 cells from 13 samples including psoriasis and wide-type mouse model. We presented a comprehensive single-cell transcriptional landscape of the skin immune cells in psoriasis, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial–mesenchymal transition and validated the results with drug verification. What’s more, we conducted a tentative exploration of the potential involving pathway and disclosed that the IL-17 signaling pathway may be the most relevant one. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive‑tract malignancy. Aberrant 3D chromatin structure contributes to enhancer landscape disruption in many cancers, but relevant research on this topic in ESCC is still lacking. In this study, CUT&Tag was performed in ESCC cell lines (KYSE30 and KYSE150) and a normal esophageal epithelial cell line (HEEC) to reveal the epigenetic landscape and identify cancer-specific enhancers. Then, we employed RNA‑seq to evaluate gene transcription and Hi‑C to explore how 3D chromatin structure regulates the epigenetic landscape and gene expression. Findings show changes in enhancer profiles and gene expression in ESCC, along with alterations in A/B compartments, TADs, and chromatin loops associated with epigenetic changes. Notably, LIMK1, EIF4H, and ABHD11 genes exhibited enhanced chromatin interactions and coexpressed patterns in the same chromatin interaction network. Our findings uncover the ESCC 3D genomic landscape and illustrate how 3D structural changes disrupt cancer‑specific enhancers and oncogene expression, providing insights into ESCC pathogenesis.