Biology subjects

Frech, S.

Publications and source records attributed to Frech, S..

3 recordsLinked to original sources

bioRxiv2026

A scRNA-seq atlas of chronic inflammatory skin diseases

Inflammatory skin diseases (ISDs) affect up to 25% of the global population. Yet, large-scale comparative single-cell RNA-sequencing (scRNA-seq) analyses between ISDs are still missing. Here, we integrated scRNA-seq datasets spanning 27 skin diseases from 50 studies, comprising over 2 million cells from 441 samples. Using the healthy skin cell atlas as reference, we could build a robust ISD atlas that enabled us to differentiate universal inflammatory signatures and disease-specific ones. This highlighted, for example, a shared gene program between keratinocytes in atopic dermatitis and parapsoriasis, not present in cutaneous T-cell lymphoma, confirms the plasticity of Th17 cells throughout ISDs, defines specific macrophage signatures in acne, and reveals a yet undescribed role of mural cells in ISDs. This demonstrates the power of the ISD atlas as a resource to resolve disease-specific immune mechanisms. The complete atlas is available through an interactive online portal at https://isd-atlas.derma.meduniwien.ac.at.

immunology↗

bioRxiv2024

A single cell and spatial genomics atlas of human skin fibroblasts in health and disease

Fibroblasts are critical cells that shape the architecture and cellular ecosystems in multiple tissues. Understanding fibroblast heterogeneity and their spatial context in health and disease has enormous clinical relevance. In this study, we constructed a spatially-resolved atlas of human skin fibroblasts from healthy skin and 23 skin disorders. We define 6 major skin fibroblast populations in health and a further three skin disease-specific fibroblast subtypes, and demonstrate the fibroblast composition in different types of skin disease. We characterise a human-specific fibroblastic reticular cell (FRC)-like subtype in the skin perivascular niche and postulate their origin from prenatal skin lymphoid tissue organiser (LTo)-like cells. We also show that inflammatory myofibroblasts (IL11+MMP1+CXCL5+IL7R+) are a conserved fibroblast subtype in inflammatory disorders and cancers across multiple human tissues. We provide a harmonised nomenclature for skin fibroblasts that integrates previous findings from human skin and other tissues.

cell biology↗

bioRxiv2023

CAF variants control the tumor-immune microenvironment and predict skin cancer malignancy

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression and treatment outcome. This study dissects the yet unresolved intra-tumoral variety of CAFs in three skin cancer types -- Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma -- at molecular and spatial single-cell resolution. By integral analysis of the fibroblasts with the tumor microenvironment, including epithelial, mesenchymal, and immune cells, we characterize three distinct CAF subtypes: myofibroblast-like RGS5+ CAFs, matrix CAFs (mCAFs), and immunomodulatory CAFs (iCAFs). Notably, large cohort tissue analysis reveals marked shifts in CAF subtype patterns with increasing malignancy. Two CAF types exhibit immunomodulatory capabilities via distinct mechanisms. mCAFs synthesize extracellular matrix and have the ability to ensheath tumor nests, potentially limiting T cell invasion in low-grade tumors. In contrast, iCAFs are enriched in late-stage tumors, especially infiltrative BCC and high-grade melanoma, and express unexpectedly high mRNA and protein levels of cytokines and chemokines, pointing to their integral role in immune cell recruitment and activation. This finding is further supported by our observation that in vitro exposure of primary healthy fibroblasts to skin cancer cell secretomes induces an iCAF-like phenotype with immunomodulatory functions. Thus, targeting CAF variants, particularly the immunomodulatory iCAF subtype, holds promise for improved efficacy of immunotherapy in skin cancers.

cancer biology↗