Single-cell RNA sequencing and machine learning provide candidate drugs against drug-tolerant persister cells in colorectal cancer

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167693 - 167693

Published: Jan. 1, 2025

Language: Английский

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Tolerogenic nanovaccines for the treatment of type I allergic diseases

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 664 - 685

Published: Feb. 17, 2025

Language: Английский

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Spatial transcriptomics in autoimmune rheumatic disease: potential clinical applications and perspectives

Inflammation and Regeneration, Journal Year: 2025, Volume and Issue: 45(1)

Published: Feb. 20, 2025

Spatial transcriptomics is a cutting-edge technology that analyzes gene expression at the cellular level within tissues while integrating spatial location information. This concept, which combines high-plex RNA sequencing with data, emerged in early 2010s. has rapidly expanded development of technologies such as situ hybridization, sequencing, barcoding, and microdissection-based methods. Each technique offers advanced mapping resolution precise assessments single-cell level. Over past decade, use on clinical samples enabled researchers to identify expressions specific diseased foci, significantly enhancing our understanding interactions disease processes. In field rheumatology, complex elusive pathophysiology diseases rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome remains challenge for personalized treatment. provides insights into how different cell populations interact synovial tissue, kidneys, salivary glands. review summarizes current autoimmune rheumatic diseases, focusing immune distribution tissues. We also explore potential from perspective discuss possibilities translating this bedside.

Language: Английский

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Mendelian Randomization Combined with Single-Cell Transcriptome Analysis Reveals the Role of the Key Gene PCLAF in the Pathogenesis of Atopic Dermatitis

Clinical Cosmetic and Investigational Dermatology, Journal Year: 2025, Volume and Issue: Volume 18, P. 867 - 882

Published: April 1, 2025

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by itching and rashes, influenced genetic, environmental, immune factors. Despite significant research, the molecular mechanisms underlying AD are not fully understood. This study aims to integrate single-cell RNA sequencing (scRNA-seq) with Mendelian Randomization (MR) uncover genetic metabolic pathways contributing AD. Data from scRNA-seq bulk datasets were analyzed identify differentially expressed genes. The edgeR package was used for differential expression analysis, candidate genes explored using MR, employing eQTL data determine causal relationships inverse variance weighted method facilitated MR while gene set enrichment analysis (GSEA) associated Single-cell performed Seurat explore cellular heterogeneity, pseudotime communication analyses conducted understand cell differentiation interactions in identified key genes-PCLAF, MICB, CHAD, CA4-linked AD, PCLAF notably acting as risk factor. These involved cycle regulation, evasion, adhesion, processes. highlighted lipid, amino acid, energy metabolism critical revealed increased especially Langerhans cells, keratinocytes, T signifying dysregulated responses pathways. Pseudotime indicated abnormal trajectories these types. Our highlights importance of pathogenesis indicating it potential target future therapeutic strategies aimed at alleviating disease addressing disruptions.

Language: Английский

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Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of systemic sclerosis

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Autoimmune rheumatic diseases present with diverse clinical manifestations that often complicate management strategies. Systemic sclerosis (SSc) is a representative disease multiple organ affecting patients worldwide, and exploring the variation of immune abnormalities in this great interest. However, previous studies have focused on diseased tissues, it remains largely unknown how cellular diversity links to heterogeneity. Here, we perform single-cell transcriptome surface proteome analyses peripheral blood mononuclear cells (PBMCs) from 21 SSc who are not receiving immunomodulatory therapy show different associated distinct abnormalities. Enrichment specific CD14⁺ monocyte subset characterized by EGR1 expression observed scleroderma renal crisis (SRC). Integrated analysis PBMCs kidney biopsy indicates directly differentiates into tissue-damaging macrophages under activation NF-κB signaling. Clinically, monocytes significantly upregulated at onset SRC decreases after treatment, suggesting its potential as biomarker for SRC. In interstitial lung (ILD), CD8⁺ T cell type II interferon signature highly enriched both tissue progressive disease, chemokine-driven migration these involved ILD progression. Thus, profiles single level reveal directions dysregulation between provide insights tailored treatment

Language: Английский

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CD142+ synovial fibroblast drives meniscus destruction in rheumatoid arthritis

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Rheumatoid arthritis (RA) induced destruction of knee joints is a common cause total arthroplasty (TKA). Although previous evidence suggests that bone and cartilage damage the main pathogenesis RA joint destruction, meniscus, special structure in joint, has been ignored. Here, we identified CD142 + synovial fibroblasts as novel SF sub-cluster located sublining layer normal osteoarthritis synovium, which elevated migrates to lining (LL) synovium. Intra-articular injection can quickly drastically meniscus but slight effect on cartilage. RNA sequencing revealed ABCC4 was highly expressed SF, pharmacological blockade by MK571 attenuated SF-induced meniscal degradation. Long-term follow-up cohort indicated enriched LL risk factor for severe eventually underwent TKA. Our results demonstrate be used an indicator assess prognosis therapeutic target inhibit damage, thereby alleviating destruction.

Language: Английский

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Bridging Gaps and Charting Future Directions in Vasculitis

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(21), P. 6571 - 6571

Published: Nov. 1, 2024

The field of vasculitis continues to evolve rapidly, driven by breakthroughs in both basic and clinical research [...].

Language: Английский

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