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Single-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis.

Dianhao Guo | Xiaokang Li | Jing Wang | Xin Liu | Yibo Wang | Shuhong Huang | Ningning Dang
Cell death & disease | 2024

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.

Pubmed ID: 38472183

Associated grants

  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82273527
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82273527
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82273527
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82273527
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82273527
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82273527
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82273527
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2022MH242
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2023QH459
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2022MH242
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2023QH459
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2022MH242
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2023QH459
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2022MH242
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2023QH459
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2022MH242
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2022MH242
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2023QH459
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2022MH242
  • Agency: Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation),
    Id: ZR2023QH459

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This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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SAMTOOLS (tool)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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HTSeq (tool)

RRID:SCR_005514

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software Python package that provides infrastructure to process data from high-throughput sequencing assays. While the main purpose of HTSeq is to allow you to write your own analysis scripts, customized to your needs, there are also a couple of stand-alone scripts for common tasks that can be used without any Python knowledge.

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NCBI Epigenomics (tool)

RRID:SCR_006151

THIS RESOURCE IS NO LONGER IN SERVICE, documented on January 19, 2022.

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Sigma-Aldrich (tool)

RRID:SCR_008988

American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.

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Trimmomatic (tool)

RRID:SCR_011848

Software Java pipeline for trimming tasks for Illumina paired end and single ended data. Flexible Trimmer for Illumina Sequence Data. Pair aware preprocessing tool optimized for Illumina next generation sequencing data. Includes several processing steps for read trimming and filtering. Operating systems Unix/Linux, Mac OS, Windows.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

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FastQC (tool)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

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HISAT2 (tool)

RRID:SCR_015530

Graph-based alignment of next generation sequencing reads to a population of genomes.

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DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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