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Dynamic interplay between IL1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration

ABSTRACT: In brief, skin resident cells were isolated from dorsal skin of mice and 10x Genomics single cell RNAseq was applied to identify distinct cell populations. Low quality cells and outliers were discarded, and only ～24,409 viable cells were used for downstream analysis. Unsupervised clustering and gene expression were visualized with the Seurat 2.0 on R studio, and assignment of cell clusters was based on expression of validated marker genes. Subsequent in-depth analysis was assisted by GENE DENOVO Inc (Guangzhou, China). Overall, we found that a specific dermal fibroblast population, with high DPP4, Sca1 and WNT2 expression, has robust capacity for adipocyte differentiation and acts key role in maintaining dermis homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE189241 | GEO | 2023/06/10

REPOSITORIES: GEO

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Dynamic interplay between IL1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration

Project description:Cells were isolated from wounded skin tissue and administered into single cell RNA transcriptome sequencing to deconstruct cell hierarchy of dermal fibroblast population and underlying regulating mechanisms. In brief, 7~9 weeks old male C57BL/6 mice were anesthetized and one full-thickness wound (1.0 cm x 0.5 cm in size) was generated on shaved dorsal skin. Animals were sacrificed at indicated intervals after and wound bed tissues were collected for cell isolation and subsequent 10x Genomics single cell RNAseq. Sequencing was performed on Illumina Novaseq6000 platform (Illumina). The generated raw gene expression matrix was converted into Seurat objects using the R package Seurat v3.0. After low quality cells and outliers were discarded, 10233 cells from non-lesional skin, 7807 cells from wound beds at post-wounding day 2 (PWD2), and 4925 cells from wound tissue at PWD7 were used for downstream analysis. Next, unsupervised clustering and gene expression were visualized with the Seurat 3.0 on R studio, and assignment and identification of cell clusters was based on the expression of validated marker genes. Subsequent in-depth analysis was assisted by GENE DENOVO Inc (Guangzhou, China). Together, our study has identified a specific dermal fibroblast population with high DPP4, Sca1 and WNT2 expression, which is committed into adipocyte upon wounding, and define the differentiation trajectory of this adipocyte precursor during skin regeneration.

2023-06-10 | GSE196800 | GEO

Defining Cell Type-specific Immune Responses in Allergic Contact Dermatitis by Single-cell Transcriptomics

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2024-08-09 | GSE224848 | GEO

Deciphering the age-dependent changes of pulmonary fibroblasts in mice by single-cell transcriptomics

Project description:In brief, lung resident cells were isolated from lung of mice and 10x Genomics single cell RNAseq was applied to identify distinct cell populations. Low quality cells and outliers were discarded, and only ～22,826 viable cells were used for downstream analysis. These included ~5,237 cells – NB(10days mice); ~4,804 cells – Adult-M(2months mice); ~6,561cells-SD-10M (10month mice) ; ~6,224cells-SD-1d5Y (18month mice). Unsupervised clustering and gene expression were visualized with the Seurat 2.0 on R studio, and assignment of cell clusters was based on expression of validated marker genes. Subsequent in-depth analysis was assisted by GENE DENOVO Inc (Guangzhou, China). Overall, we found that a specific lung fibroblast population, We present a single-cell transcriptomic atlas encompassing lung tissues derived from mice at various stages of aging, uncovering substantial shifts in fibroblast differentiation and immune regulation throughout the aging process.

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Identification of a mesenchymal progenitor cell hierarchy in adipose tissue (Bulk RNA-seq)

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Identification of a mesenchymal progenitor cell hierarchy in adipose tissue (scRNA-seq)

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2020-05-26 | PXD014019 | Pride

Repurposing DPP4-Inhibition to Improve Hair Follicle Activation and Regeneration

Project description:Skin-injury and several diseases elicit fibrosis and induce hair follicle (HF)-growth arrest and loss. Resulting alopecia and disfiguration represent a severe burden for patients both physically and psychologically. Reduction of pro-fibrotic factors such as DPP4 might be a strategy to tackle this issue. We demonstrate DPP4-overrepresentation in settings with HF-growth arrest (telogen), HF-loss and non-regenerative wound areas in mice skin and human scalp. Topical DPP4-inhibition (DPP4i) with FDA/EMA-approved Sitagliptin (Sit) on preclinical models of murine HF-activation/regeneration results in accelerated anagen-progress, while treatment of wounds with Sit results in reduced expression of fibrosis markers, increased induction of anagen around wounds, and HF-regeneration in the wound center. These effects are associated with higher expression of Wnt-target Lef1, known to be required for HF-anagen (HF-activation)/regeneration. Sit-treatment decreases pro-fibrotic signaling in the skin, induce a differentiation trajectory of HF-cells, and activate Wnt-targets related to HF-activation/growth but not those supporting fibrosis. Taken together, our study demonstrates a role for DPP4 in HF biology and shows how DPP4i, currently used as oral medication to treat diabetes, could be repurposed into a topical treatment agent to potentially reverse HF-loss in alopecia and after injury.

2023-05-02 | GSE230514 | GEO

Scar management through modulation of the fibrotic microenvironment by CAR-Trem2-macrophages (scRNA-seq)

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2024-09-24 | GSE248960 | GEO

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