Single cell transcriptomics of human epidermis identifies basal stem cell transition states

Area of Science:

• Dermatology
• Stem Cell Biology
• Genomics

Background:

• The epidermis, crucial for barrier and appendage formation, relies on stem cells whose differentiation pathways remain incompletely understood.
• Understanding epidermal stem cell heterogeneity is vital for addressing skin development and homeostasis.

Purpose of the Study:

• To investigate the heterogeneity of basal stem cells in human interfollicular epidermis.
• To elucidate the differentiation pathways and roles of distinct epidermal stem cell populations.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was employed to analyze basal stem cell populations.
• Cell-cell communication modeling, pseudotime analysis, RNA velocity, and cellular entropy analyses were utilized.
• Human skin equivalents were used to validate findings related to stem cell gene expression.

Main Results:

• Four spatially distinct basal stem cell populations were identified within the human interfollicular epidermis.
• These populations are located at the top/bottom of rete ridges and in transitional positions.
• Cell-cell communication modeling identified basal cells as key signaling hubs.
• Hierarchical differentiation pathways were revealed, supporting multi-stem cell homeostasis models.
• Transitional basal stem cells were identified as stable states crucial for epidermal stratification.

Conclusions:

• Basal stem cell heterogeneity is critical for maintaining epidermal homeostasis and proper skin stratification.
• Alterations in transitional basal stem cell genes lead to significant skin thinning, confirming their essential role.
• These findings provide new insights into the complex mechanisms governing epidermal development and stem cell function.