Characterization of the epidermal-dermal junction in hiPSC-derived skin organoids

• Main Authors: Chuva de Sousa Lopes, S.M (Author), Freund, C. (Author), Fuentes, I. (Author), Gidrol, X. (Author), Janssen, H. (Author), Mummery, C.L (Author), Pitaval, A. (Author), Rachidi, W. (Author), Ramovs, V. (Author), Raymond, K. (Author)
• Format: Article
• Language: English
• Published: Cell Press 2022
• Subjects: collagen; epidermal-dermal junction; hiPSC-derived hair-bearing skin organoids
• Online Access: View Fulltext in Publisher
• ISBN: 22136711 (ISSN)
• DOI: 10.1016/j.stemcr.2022.04.008

Human induced pluripotent stem cell (hiPSC)-derived hair-bearing skin organoids offer exciting new possibilities for modeling diseases like epidermolysis bullosa (EB). These inherited diseases affect 1 in 30,000 people worldwide and result from perturbed expression and/or structure of components of the epidermal-dermal junction (EDJ). To establish whether hiPSC-derived skin organoids might be able to capture salient features of EB, it is thus important to characterize their EDJ. Here, we report successful generation of hair-bearing skin organoids from two hiPSC lines that exhibited fully stratified interfollicular epidermis. Using immunofluorescence and electron microscopy, we showed that basal keratinocytes in organoids adhere to laminin-332 and type IV collagen-rich basement membrane via type I hemidesmosomes and integrin β1-based adhesion complexes. Importantly, we demonstrated that EDJs in organoids are almost devoid of type VII collagen, a fibril that mediates anchorage of the epidermis to dermis. This should be considered when using skin organoids for EB modeling. © 2022 The Author(s)