Enhanced Differentiation Potential of Pigmented Human Epidermal Equivalents

    May 2025
    Yunlong Jia, Julia Bajsert, Miguel Pérez‐Aso, Scott X. Atwood
    TLDR PmtHEE is a better model for studying pigmented skin because it includes melanocytes and shows improved cell differentiation.
    The study introduces a pigmented human epidermal equivalent (PmtHEE) that incorporates melanocytes into the epidermis, addressing the limitations of most 3D human skin equivalents that lack melanocytes. Using single-cell RNA sequencing, PmtHEE was compared with neonatal foreskin epidermis and a fibroblast-containing human skin equivalent model. PmtHEE demonstrated a higher proportion of differentiated cells and unique cell state transition paths that mimic in vivo trajectories. Additionally, a shared L1CAM-EZR-driven signaling network was identified, mediating melanocyte-to-keratinocyte communication and supporting epidermal differentiation. Overall, PmtHEE offers a distinct and physiologically relevant model of pigmented skin with enhanced differentiation potential compared to traditional in vitro systems.
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