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Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [ATAC-seq]

ABSTRACT: By using dual-omics profiling for both chromatin accessibility and gene expression as well as CUT&RUN sequencing for chromatin modification states, we identified that numerous disease-associated inflammatory enhancers were epigenetically activated and co-exist with the transcriptional states of their target genes in basal progenitor cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226424 | GEO | 2023/10/18

REPOSITORIES: GEO

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Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [CUT&RUN]

Project description:1) By using dual-omics profiling for both chromatin accessibility and gene expression as well as CUT&RUN sequencing for chromatin modification states, we identified that numerous disease-associated inflammatory enhancers were epigenetically activated and co-exist with the transcriptional states of their target genes in basal progenitor cells. 2) By using CUT&RUN sequencing , we identified numerous S100A8 binding DNA sequences in HS epidermal cells.

2023-10-18 | GSE226425 | GEO

Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [RNA-seq]

Project description:By using dual-omics profiling for both chromatin accessibility and gene expression as well as CUT&RUN sequencing for chromatin modification states, we identified that numerous disease-associated inflammatory enhancers were epigenetically activated and co-exist with the transcriptional states of their target genes in basal progenitor cells.

2023-10-18 | GSE226426 | GEO

Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-17 | GSE226428 | GEO

Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [scRNA-seq]

Project description:In this study, we used single-cell RNA-sequencing to reveal how cellular heterogeneity of Hidradenitis Suppurativa (HS) lesional epidermis was reshaped at the transcriptional level. By comparison with healthy interfollicular epidermal basal cells, in HS we revealed marked gene signatures centered on mitotic chromosome segregation, DNA replication and repair as well as cell-cell adhesion and chromatic remodeling. Combing the pseudotime-ordered single-cell trajectory with the spatial localization analysis of defined basal cells, we further identified and validated a global alteration in cellular diversity within HS epidermis characterized by basal I-III cells hyperproliferation, concomitant decreases in superbasal keratinocytes, and phenotypic shifts toward the S100A cluster highly expressing pro-inflammatory genes S100A7/8/9. Cell-cell communication modeling suggested that HS BIII keratinocytes and S100A population serve as a crucial source to trigger IL-1 and IL-10 inflammatory cascades in the disease progression.

2023-10-18 | GSE226427 | GEO

Epigenetic switch reshapes epithelial progenitor cell signatures and drives inflammatory pathogenesis in hidradenitis suppurativa.

Project description:Hidradenitis suppurativa (HS) is a complex inflammatory skin disease with undefined mechanistic underpinnings. Here, we investigated HS epithelial cells and demonstrated that HS basal progenitors modulate their lineage restriction and give rise to pathogenic keratinocyte clones, resulting in epidermal hyperproliferation and dysregulated inflammation in HS. When comparing to healthy epithelial stem/progenitor cells, in HS, we identified changes in gene signatures that revolve around the mitotic cell cycle, DNA damage response and repair, as well as cell-cell adhesion and chromatin remodeling. By reconstructing cell differentiation trajectory and CellChat modeling, we identified a keratinocyte population specific to HS. This population is marked by S100A7/8/9 and KRT6 family members, triggering IL1, IL10, and complement inflammatory cascades. These signals, along with HS-specific proinflammatory cytokines and chemokines, contribute to the recruitment of certain immune cells during the disease progression. Furthermore, we revealed a previously uncharacterized role of S100A8 in regulating the local chromatin environment of target loci in HS keratinocytes. Through the integration of genomic and epigenomic datasets, we identified genome-wide chromatin rewiring alongside the switch of transcription factors (TFs), which mediated HS transcriptional profiles. Importantly, we identified numerous clinically relevant inflammatory enhancers and their coordinated TFs in HS basal CD49fhigh cells. The disruption of the S100A enhancer using the CRISPR/Cas9-mediated approach or the pharmacological inhibition of the interferon regulatory transcription factor 3 (IRF3) efficiently reduced the production of HS-associated inflammatory regulators. Our study not only uncovers the plasticity of epidermal progenitor cells in HS but also elucidates the epigenetic mechanisms underlying HS pathogenesis.

| S-EPMC10710069 | biostudies-literature

Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [CUT&RUN]

Project description:Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [CUT&RUN]

| PRJNA940164 | ENA

Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa

Project description:Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa

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Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [RNA-seq]

Project description:Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [RNA-seq]

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Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [ATAC-seq]

Project description:Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [ATAC-seq]

| PRJNA940165 | ENA

Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [scRNA-seq]

Project description:Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [scRNA-seq]

| PRJNA940167 | ENA

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