Advanced Single-Cell Sequencing in Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular Genetics and Genetic Diseases".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 890

Special Issue Editor


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Guest Editor
Pulmonary Division, Indiana University School of Medicine, Indianapolis, IN, USA
Interests: single-cell sequencing; spatial transcriptomics

Special Issue Information

Dear Colleagues,

For this Special Issue, “Advanced Single-Cell Sequencing in Diseases”, we welcome studies that apply single-cell and spatial transcriptomic analyses to explore the cellular diversity and molecular mechanisms underlying various diseases. We invite submissions that use either newly generated or publicly available single-cell datasets to perform analyses such as clustering, annotation, and visualization with UMAP, DotPlot, FeaturePlot, or comparable approaches. Studies utilizing Seurat, Scanpy, or related bioinformatics frameworks for data processing, integration, and interpretation are highly encouraged. Papers comparing disease and control conditions, identifying cell-type-specific gene expression changes, or characterizing novel cellular subpopulations across tissues and models are particularly welcome. The scope includes all disease areas and experimental systems that employ single-cell data to draw biological conclusions. Our aim is to compile a collection of data-driven analyses demonstrating how single-cell technologies and computational tools can advance our understanding of disease biology.

We look forward to receiving your contributions.

Dr. Sedat Kacar
Guest Editor

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Keywords

  • single-cell sequencing
  • bioinformatics analysis
  • spatial transcriptomics
  • cellular heterogeneity
  • data-driven discovery
  • disease biology

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Published Papers (1 paper)

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Research

23 pages, 8470 KB  
Article
Cell-Type-Resolved Acetylation Regulator Atlas Defines Immune Endotypes and Druggable Vulnerabilities in Psoriasis
by Mengji Xie, Xiaoxuan Ma, Ying Zhang, Le Kuai, Ying Luo, Jiankun Song, Xiaojie Ding, Yi Ru, Yue Luo, Xiaoya Fei, Seokgyeong Hong, Guoshu Deng, Yonghua Su, Ruiping Wang, Bin Li, Yanwei Xiang, Miao Li and Mi Zhou
Biomedicines 2026, 14(4), 804; https://doi.org/10.3390/biomedicines14040804 - 1 Apr 2026
Viewed by 614
Abstract
Background: Psoriasis frequently relapses after treatment withdrawal, consistent with persistent epigenetic programs in lesional immune cells. Lysine acetylation is a reversible regulatory layer linking chromatin accessibility, transcription factor activity, and immune-cell effector programs; yet, its cell-type-resolved landscape and clinical stratification value in psoriasis [...] Read more.
Background: Psoriasis frequently relapses after treatment withdrawal, consistent with persistent epigenetic programs in lesional immune cells. Lysine acetylation is a reversible regulatory layer linking chromatin accessibility, transcription factor activity, and immune-cell effector programs; yet, its cell-type-resolved landscape and clinical stratification value in psoriasis remain incompletely defined. Methods: We integrated four bulk transcriptome cohorts of psoriatic and healthy skin (746 psoriasis, 515 controls) with two public skin scRNA-seq datasets. A diagnostic acetylation-regulator signature was derived from 33 curated acetylation regulators, and acetylation endotypes were defined by unsupervised clustering. The cell-type-specific expression was mapped at the single-cell resolution. Key regulators were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an imiquimod-induced psoriasis-like mouse model, and further verified in an independent dataset (GSE136757). Motif enrichment and drug–target mining were used to prioritize transcriptional regulators and candidate epigenetic therapeutics. Results: Sixteen acetylation regulators were differentially expressed in bulk skin, with histone deacetylase (HDAC1) showing the strongest upregulation and lysine acetyltransferase (KAT2A) the strongest downregulation. A 13-gene acetylation signature discriminated psoriasis from controls (area under the curve, AUC 0.886) and separated lesional samples into two acetylation endotypes with divergent pathway states (hypoxia–glycolysis versus oxidative-stress-dominated programs). Single-cell mapping demonstrated immune-restricted acetylation modules, including CREB binding protein (CREBBP)-enriched neutrophils, histone deacetylase 1 (HDAC1)-high cluster of differentiation (CD)8+ T cells, and lysine acetyltransferase 6A (KAT6A)/lymphoid enhancer binding factor (LEF1)-enriched CD4+ and regulatory T cell (Treg) subsets, coincident with interleukin (IL)-17-related inflammatory programs. In mice, qRT-PCR confirmed the coordinated dysregulation of hub genes and highlighted Hnf1a and Kat6a as reproducible candidates. External validation using the GSE136757 dataset further supports their robust diagnostic performance. Motif analysis nominated interferon regulatory factor (IRF4), YY transcription factor (YY2), and zinc finger protein (ZNF404) as putative transcriptional mediators downstream of acetylation programs, and drug–target mining prioritized epigenetic compounds with subtype-relevant potential, including histone deacetylase (HDAC) inhibitors (e.g., entinostat) and the p300/CREB binding protein (CBP) inhibitor A485. Conclusions: This integrative atlas links acetylation regulators to specific immune compartments, defines acetylation endotypes associated with distinct inflammatory programs, and provides a rationale for stratified epigenetic target selection in psoriasis. Full article
(This article belongs to the Special Issue Advanced Single-Cell Sequencing in Diseases)
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