Enhanced Differentiation Potential of Pigmented Human Epidermal Equivalents
August 2026
pigmented human epidermal equivalent melanocytes 3D human skin equivalents single-cell RNA sequencing neonatal foreskin epidermis fibroblast-containing human skin equivalent differentiated cells cell state transition L1CAM-EZR signaling network melanocyte-to-keratinocyte communication epidermal differentiation pigmented skin model skin equivalents RNA sequencing skin differentiation
Studysummary This study utilized a pigmented human epidermal equivalent model to incorporate melanocytes into the epidermis and found enhanced differentiation potential compared to conventional in vitro systems, reflecting in vivo cellular trajectories and highlighting melanocyte-to-keratinocyte communication pathways. Our plain-language summary of this paper — not a Tressless recommendation.
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.
