Enhanced differentiation potential of pigmented human epidermal equivalents

Melanocyte-keratinocyte interactions are essential for controlling melanogenesis and preserving epidermal balance. However, many 3D human skin substitutes lack melanocytes, restricting their usefulness for pigmentation research. To overcome this limitation, researchers created a pigmented human epidermal equivalent (PmtHEE) that integrates melanocytes into the epidermis.

Through single-cell RNA sequencing (scRNA-seq), PmtHEE was examined and compared to neonatal foreskin epidermis (FsEpi) and a model with fibroblasts (FibHSE). PmtHEE demonstrated a greater proportion of differentiated cells and unique cellular transformation routes that mirror potential in vivo pathways. By using exSigNet, the study also identified an inferred L1CAM-EZR-driven external signaling network that could impact keratinocyte differentiation in both FsEpi and PmtHEE.

In summary, PmtHEE offers a distinctive and biologically relevant model of pigmented skin, potentially exhibiting a superior differentiation capacity compared to traditional laboratory models. The research was funded by the National Science Foundation and the Generalitat de Catalunya. Both Yunlong Y. Jia and Julia Bajsert made equal contributions to the study.

The Department of Developmental and Cell Biology at the University of California, Irvine, UC Irvine, Irvine, CA, USA; the Center for Complex Biological Systems, Chao Family Comprehensive Cancer Center, UC Irvine, CA, USA; and the NSF-Simons Center for Multiscale Cell Fate Research, UC Irvine, CA, USA were involved in the research.

Miguel Perez-Aso and Scott X. Atwood are employees of Provital, S.A., located in Barcelona, Spain. None of the authors have declared any conflicts of interest. This article is licensed under a Creative Commons Attribution 4.0 International License, enabling the use, sharing, adaptation, distribution, and reproduction in any medium or format, as long as appropriate credit is given to the original author(s) and the source, a link to the Creative Commons license is provided, and any changes are noted.