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Updated: Jun 1, 2026

Cultivating a Three-dimensional Reconstructed Human Epidermis at a Large Scale
Published on: May 28, 2021
Compartmentalization of the human stratum corneum by persistent tight junction-like structures
Marek Haftek1, Sylvie Callejon, Yongoua Sandjeu
1Université Lyon 1, EA4169 Normal and pathological functions of skin barrier, Lyon, France. marek.haftek@univ-lyon1.fr
Insights
Tight junction (TJ) proteins persist in the stratum corneum (SC), reinforcing corneocyte connections and sealing intercorneocyte spaces. This structural persistence may influence the SC
Area of Science:
- Dermatology
- Cell Biology
- Biophysics
Background:
- Tight junctions (TJs) are crucial for epidermal barrier function in living skin layers.
- Previous studies indicated TJ-like structures at the stratum granulosum (SG) of human epidermis.
Purpose of the Study:
- To investigate the presence and role of TJ-derived structures within the stratum corneum (SC) of adult human epidermis.
- To examine the structural contribution of TJs to corneocyte interactions and epidermal barrier integrity.
Main Methods:
- Standard and immunoelectron microscopy were employed.
- Analysis of purified cornified envelopes from plantar SC.
Main Results:
- TJ proteins, including claudin-1, were detected in the lower SC and purified cornified envelopes.
- Molecular fusion points between corneocyte lipid envelopes were observed, particularly at the top of lateral membranes.
- These structures seal intercorneocyte spaces and form membrane interdigitations.
Conclusions:
- TJ-like structures persist in the SC, reinforcing corneocyte contacts and contributing to epidermal barrier function.
- The presence of TJs in the SC may compartmentalize extracellular spaces, influencing the differential degradation of corneodesmosomes.
- This compartmentalization could explain variations in degradation rates during physiological desquamation.
Abstract:
Several tight junction (TJ) proteins were detected in the living layers of adult human epidermis, and TJ-like membrane ridges were observed at the top of the stratum granulosum (SG) in freeze-fracture studies. We applied standard and immunoelectron microscopy to look for TJ-derived structures in the stratum corneum (SC) of human adult epidermis and in cornified envelopes purified from the plantar SC. Besides confirming claudin-1 labelling in the proximity of SG desmosomes, we also observed immunolocalization near corneodesmosomes in the lower SC. In addition, TJ proteins were consistently detected in the purified cornified envelopes. Lateral but not horizontal walls of the corneocytes showed frequent points of molecular fusion between lipid envelopes. These structural associations were very frequently localized at the top of the lateral corneocyte membranes, thus sealing the extremities of lateral intercorneocyte spaces. We propose that TJ-like structures persist in the SC and contribute to the reinforcement of lateral contacts and to the formation of membrane interdigitations between corneocytes. Their presence could contribute to subdivision of the extracellular spaces of SC into consecutive individualized compartments. Intercellular lipids, enzymes and other (glyco)protein content could thus evolve in the keratinized epidermal layer at different paces, as preprogrammed in the underlying living cells and influenced by the environment, e.g. humidity. Such situation might explain differences in the degradation rates between the 'peripheral' and the 'non-peripheral' corneodesmosomes observed during physiological desquamation, as previously suggested by us and others.
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