Deciphering Fibroblast Regulatory Mechanisms in Murine Neonatal and Adult Epidermal Regeneration

Date of Award

Spring 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Genetics

First Advisor

Greco, Valentina

Abstract

Highly regenerative organs, like the skin, depend on coordinated cell interactions to sustain continuous cellular turnover. In vitro, skin fibroblasts promote epidermal stem cell expansion and differentiation. Yet, it remains elusive how fibroblasts regulate epidermal stem cell behaviors and tissue architecture in vivo. Here, we show that in neonatal stages, reducing fibroblasts increases epidermal basal cell density and thickens the epidermal architecture. This is associated with an altered basement membrane (BM) that is laminin enriched. Notably, reducing Collagen I in neonatal skin does not replicate the epidermal basal cell density and architecture changes observed with fibroblast reduction. In contrast, reducing fibroblasts in adult mice results in a thinner epidermal architecture when BM and collagen assembly are largely complete. Our work demonstrates distinct, stage-dependent regulatory effects of fibroblasts on epidermal architecture in vivo that is likely driven by BM remodeling rather than collagen assembly.

This document is currently not available here.

Share

COinS