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<p>Melanocyte-keratinocyte interactions are vital for regulating melanogenesis and maintaining epidermal homeostasis. However, most 3D human skin equivalents lack melanocytes, limiting their relevance for pigmentation studies. To address this, we utilized a pigmented human epidermal equivalent (PmtHEE) that incorporates melanocytes into the epidermis. Using single-cell RNA sequencing (scRNA-seq), we characterized PmtHEE and compared it with neonatal foreskin epidermis (FsEpi) and a fibroblast-containing human skin equivalent model (FibHSE). PmtHEE showed a higher proportion of differentiated cells and model-specific cell state transition paths that reflect possible in vivo trajectories. We further uncovered an inferred L1CAM-EZR-driven external signaling network using exSigNet in FsEpi and PmtHEE that may influence keratinocyte differentiation. Altogether, PmtHEE provides a distinct and physiologically relevant model of pigmented skin, with likely enhanced differentiation potential compared to conventional in vitro systems.</p>

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Enhanced differentiation potential of pigmented human epidermal equivalents

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月4日

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  • Yunlong Y. Jia,
  • Julia Bajsert,
  • Arinnae I. Kurdian,
  • Jessica Shiu,
  • Miguel Perez-Aso,
  • Scott X. Atwood

摘要

Melanocyte-keratinocyte interactions are vital for regulating melanogenesis and maintaining epidermal homeostasis. However, most 3D human skin equivalents lack melanocytes, limiting their relevance for pigmentation studies. To address this, we utilized a pigmented human epidermal equivalent (PmtHEE) that incorporates melanocytes into the epidermis. Using single-cell RNA sequencing (scRNA-seq), we characterized PmtHEE and compared it with neonatal foreskin epidermis (FsEpi) and a fibroblast-containing human skin equivalent model (FibHSE). PmtHEE showed a higher proportion of differentiated cells and model-specific cell state transition paths that reflect possible in vivo trajectories. We further uncovered an inferred L1CAM-EZR-driven external signaling network using exSigNet in FsEpi and PmtHEE that may influence keratinocyte differentiation. Altogether, PmtHEE provides a distinct and physiologically relevant model of pigmented skin, with likely enhanced differentiation potential compared to conventional in vitro systems.