Skin fibroblast functional heterogeneity in health and disease

Abstract

Fibroblasts are the major cell population of connective tissue, including the skin dermis, and are best known for their function in depositing and remodelling the extracellular matrix. Besides their role in extracellular matrix homeostasis, fibroblasts have emerged as key players in many biological processes ranging from tissue immunity and wound healing to hair follicle development. Recent advances in single‐cell RNA‐sequencing technologies have revealed an astonishing transcriptional fibroblast heterogeneity in the skin and other organs. A key challenge in the field is to understand the functional relevance and significance of the identified new cell clusters in health and disease. Here, we discuss the functionally distinct fibroblast subtypes identified in skin homeostasis and repair and how they evolve in fibrotic disease conditions, in particular keloid scars and cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Suitably Incorporated Hydrophobic, Redox-Active Drug in Poly Lactic Acid-Graphene Nanoplatelet Composite Generates 3D-Printed Medicinal Patch for Electrostimulatory Therapeutics

“…Fibroblasts cells (NIH3T3), because of being a significant population of skin tissue, was taken as healthy control for this study. 70 The experimental set up has been represented in Figure 5a, where 3D-est-MediPatch and other necessary controls like only niclosamide, 3DP hl-PLGR composite were applied to each well filled with PBS and then electrical stimulation was applied. It was observed that 3 days treatment of 3D printed Nic-hl-PLGR with electrical treatment could produce ∼43% cell death in A375 cells which was significantly lesser than the treatment with only niclosamide which was ∼79% in the presence of electrical current Figure 5b.…”

“…The effect of niclosamide release through the direct application of electrical current from 3D- est -MediPatch was investigated in vitro in a malignant melanoma cell (A375). Fibroblasts cells (NIH3T3), because of being a significant population of skin tissue, was taken as healthy control for this study . The experimental set up has been represented in Figure a, where 3D- est -MediPatch and other necessary controls like only niclosamide, 3DP hl -PLGR composite were applied to each well filled with PBS and then electrical stimulation was applied.…”

Single-cell sequencing highlights heterogeneity and malignant progression in actinic keratosis and cutaneous squamous cell carcinoma

“…The functional analysis of Fib4 markers indicated that this group was related to cell adhesion and immune cell migration ( Figure 7—figure supplement 2 ). The secretory reticular fibroblasts have been reported contributing to ECM organization and immunomodulatory ( Bensa et al, 2023 ). Fib5 specifically expressed typical mesenchymal fibroblast markers like ASPN, OGN, and TNN ( Ascensión et al, 2021 ).…”

Recent Advances in Pathology: the 2023 Annual Review Issue of The Journal of Pathology

“…The final review in this section relates to the increasing evidence for distinct subtypes of fibroblasts with diverse functional properties. In their article, Bensa, Tekkela, and Rognoni from the Blizard Institute in London, UK, concentrate on fibroblast subtypes in the skin [8]. They review the transcriptional heterogeneity of fibroblasts in skin and other tissues discovered by single cell RNA sequencing, and the diverse roles of fibroblast subtypes, including their well‐known roles in extracellular matrix remodelling and their less‐appreciated functions in immune responses, wound healing, and hair follicle development.…”