Characterization of the epidermal-dermal junction in hiPSC-derived skin organoids
Summary
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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
| Authors | Ramovs V, Janssen H, Fuentes I, Pitaval A, Rachidi W, Chuva de Sousa Lopes SM, Freund C, Gidrol X, Mummery CL, Raymond K |
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| Journal | Stem cell reports |
| Publication Date | 2022 Jun 14;17(6):1279-1288 |
| PubMed | 35561682 |
| PubMed Central | PMC9213820 |
| DOI | 10.1016/j.stemcr.2022.04.008 |