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Hegazy, A. M.

Publications and source records attributed to Hegazy, A. M..

2 recordsLinked to original sources
bioRxiv2026

Inflammatory IL-1 signaling remodels epidermal stem cell compartments by suppressing Wnt activity

The skin epidermis is maintained by spatially organized stem cell populations with distinct cellular dynamics; however, how inflammation affects this heterogeneity remains largely unknown. Here, we demonstrate that acute skin inflammation alters epidermal stem cell compartments through IL-1-mediated suppression of canonical Wnt signaling. Lineage tracing in inflamed mouse skin revealed that slow-cycling Dlx1+ epidermal stem cell clones persist, whereas fast-cycling Slc1a3+ clones decline through enhanced differentiation and lineage conversion, driving the reorganization of epidermal stem cell compartments. IL-1 signaling is both necessary and sufficient for this change: administration of IL-1/{beta} recapitulates these effects, while transgenic induction of the IL-1 decoy receptor preserves the balance of stem cell populations. IL-1 suppresses canonical Wnt activity in both the mouse epidermis and human keratinocytes, and Wnt ligand administration restores the fast-cycling compartment in vivo. Together, these results identify a reversible IL-1-Wnt axis that governs inflammation-induced stem cell plasticity and spatial tissue remodeling. HighlightO_LIInflammation induces reversible remodeling of epidermal stem cell compartments C_LIO_LIDistinct epidermal stem cell populations exhibit differential responses to inflammation C_LIO_LIIL-1 suppresses canonical Wnt signaling, thereby biasing fast-cycling stem cell behavior C_LIO_LIReactivation of Wnt signaling restores stem cell population balance under inflammatory conditions C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/704488v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@e430e5org.highwire.dtl.DTLVardef@1464550org.highwire.dtl.DTLVardef@70ba1borg.highwire.dtl.DTLVardef@ca502c_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗
bioRxiv2025

Integrin-binding matricellular protein fibulin-5 maintains epidermal stem cell heterogeneity during skin aging

The extracellular matrix (ECM) is crucial in building the extracellular environment and translating extracellular information into biochemical signals that sustain organ functions. Fibulin-5 (Fbln5) is a multifunctional ECM protein essential for forming elastic fibers and regulating cellular functions by binding to integrins. While fibulin-5 expression decreases with age in human skin, the functional implications of this decrease, particularly in epidermal stem cell regulation, have remained largely unexplored. Here, we find that the knocking out of Fbln5 in mice results in early impairments of epidermal stem cell properties, similar to the chronological aging of the skin. The Fbln5 deficiency suppresses the expression of integrins and other cell junction proteins, leading to the inactivation of YAP signaling in epidermal stem cells. This reduction in YAP signaling results in the downregulation of the fast-cycling epidermal stem cell marker SLC1A3 in human skin and primary keratinocytes. These results suggest that, in addition to its known function in elastic fiber formation, fibulin-5 also plays a critical role in regulating the balance of epidermal stem cell populations during skin aging and coordinating the crosstalk between the extracellular environment and intracellular signaling.

developmental biology↗