Keloid transcriptomics reveal heterogeneity in fibroblast subtype enrichment, gene expression, and immune cell responses
- 1Henry Ford Health
Abstract
Keloid disease (KD) is a fibroproliferative skin disorder resulting from abnormal scar formation that causes pain, itching, and decreased quality of life. While multiple KD transcriptomic studies exist, the influence of cell type composition on bulk tissue gene expression is unknown. We characterized fibroblast subtype and immune cell enrichment using bulk RNA-Seq of head and neck keloid and matched adjacent normal skin tissue (MANST) from 14 patients (10 African American and 4 European American). Cell type enrichment was calculated by single sample gene set enrichment analysis. Linear mixed-effects models were employed for 1) differential cell type enrichment across tissue, 2) tissue type-specific associations between fibroblast subtypes and immune cells, and 3) differentially expressed genes (DEGs) across tissue. Validation was conducted in an independent cohort of 8 African Americans. Three fibroblast subtypes and 14 immune cell types were differentially enriched across tissue type. Further, 17 tissue type-specific fibroblast subtype-immune cell enrichment associations were identified, with 14 exhibiting decreased association in keloid tissue relative to MANST. After adjustment for cell type enrichment, MIR31HG and NR4A2 were significant DEGs with the largest positive and negative fold-changes, respectively. By considering cell type enrichment, underlying keloid tissue-specific cell type and gene expression associations were revealed.
Related
- A significant enrichment that is not: spatial nulls, co-expression, and the imaging transcriptomics of EEG alpha-power genetics
- Differential Gene Expression and Functional Enrichment Analysis of Breast Tumor and Normal Tissue RNA-seq Data: A Reanalysis of GEO Dataset GSE210787
- A Full Spectrum Fibroblast Profiling Panel Reveals Phenotypic and Metabolic Heterogeneity of Cancer-Associated Fibroblasts at the Single-Cell Level
- Spatial transcriptomic mapping of anti-MDA5 dermatomyositis reveals perivascular enrichment of type I interferon responses and immune activation
- Single-cell atlas of urethral stricture reveals fibroblast, mast cell, and macrophage heterogeneity with candidate regulators
BibTeX
@misc{panzer2026keloid,
title = {{Keloid transcriptomics reveal heterogeneity in fibroblast subtype enrichment, gene expression, and immune cell responses}},
author = {J. J. Panzer and M. Pan and M. Nair and I. M. Loveless and I. Adrianto and L. Huang and D. Chitale and R. Francescone and D. B. Vendramini-Costa and C. de Guzman Strong and A. M. Levin and L. R. Jones},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.747090},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.747090v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Keloid transcriptomics reveal heterogeneity in fibroblast subtype enrichment, gene expression, and immune cell responses
AU - J. J. Panzer
AU - M. Pan
AU - M. Nair
AU - I. M. Loveless
AU - I. Adrianto
AU - L. Huang
AU - D. Chitale
AU - R. Francescone
AU - D. B. Vendramini-Costa
AU - C. de Guzman Strong
AU - A. M. Levin
AU - L. R. Jones
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.747090
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.747090v1
AB - Keloid disease (KD) is a fibroproliferative skin disorder resulting from abnormal scar formation that causes pain, itching, and decreased quality of life. While multiple KD transcriptomic studies exist, the influence of cell type composition on bulk tissue gene expression is unknown. We characterized fibroblast subtype and immune cell enrichment using bulk RNA-Seq of head and neck keloid and matched adjacent normal skin tissue (MANST) from 14 patients (10 African American and 4 European American). Cell type enrichment was calculated by single sample gene set enrichment analysis. Linear mixed-effects models were employed for 1) differential cell type enrichment across tissue, 2) tissue type-specific associations between fibroblast subtypes and immune cells, and 3) differentially expressed genes (DEGs) across tissue. Validation was conducted in an independent cohort of 8 African Americans. Three fibroblast subtypes and 14 immune cell types were differentially enriched across tissue type. Further, 17 tissue type-specific fibroblast subtype-immune cell enrichment associations were identified, with 14 exhibiting decreased association in keloid tissue relative to MANST. After adjustment for cell type enrichment, MIR31HG and NR4A2 were significant DEGs with the largest positive and negative fold-changes, respectively. By considering cell type enrichment, underlying keloid tissue-specific cell type and gene expression associations were revealed.
ER -