Mitotic Diversity in Homeostatic Human Interfollicular Epidermis

Area of Science:

• Dermatology
• Cell Biology
• Tissue Engineering

Background:

• Human epidermis homeostasis and proliferation regulation remain incompletely understood.
• Mitotic orientation's role in tissue regulation requires further investigation.

Purpose of the Study:

• To systematically assess mitotic orientations during human epidermal development and regeneration.
• To investigate the role of Numb protein in keratinocyte division and epidermal homeostasis.

Main Methods:

• Utilized human long-term skin equivalents for systematic mitotic assessment.
• Analyzed mitotic orientations (horizontal, oblique, perpendicular, suprabasal) and keratin K10 expression.
• Investigated Numb protein distribution and function using CRISPR/Cas9 knockdown and live cell imaging.

Main Results:

• Identified four distinct mitotic orientations in human epidermis, linked to symmetric/asymmetric division and differentiation.
• Observed suprabasal mitoses, many committed to differentiation (Keratin K10-positive).
• Found Numb protein asymmetrically distributed in some mitoses, particularly under low-calcium conditions, but Numb deletion did not affect proliferation.

Conclusions:

• Spatial mitotic organization is integral to human epidermal tissue homeostasis.
• Numb protein is not essential for the general control of keratinocyte proliferation or epidermal regeneration.