Cell-cell adhesion-induced patterning in keratinocytes can be explained by just starvation and strong adhesion researchers find.
Hokkaido University researchers have shown that the patterning of keratinocytes due to cell-cell adhesion can be explained solely by starvation and robust adhesion.
Fingerprints serve as a prominent example of how epithelial cells can form distinct patterns. Keratinocytes are the primary cells in the epithelium and can create patterns on both microscopic and macroscopic scales. Although numerous factors influencing this pattern formation have been identified, the precise mechanisms driving the process remain unclear.
A research team, headed by Associate Professor Ken Natsuga from the Faculty of Medicine at Hokkaido University, has uncovered that cell-cell adhesion is a key factor in the pattern formation of keratinocytes. Their discoveries were published in the journal Life Science Alliance.
“In this study, we utilized an immortalized keratinocyte cell line known as HaCaT, which maintains the characteristics of normal keratinocytes,” Natsuga noted. “To ensure the reliability of our findings, we created single-cell cultures from this cell line.”
The researchers observed that pattern formation occurred in both the original diverse cell line and in the single-cell-derived cultures. Throughout the culturing process, the keratinocytes moved randomly and began to spontaneously create areas of high and low cell density, resulting in pattern formation.
Starvation had a significant impact on the formation of these patterns. Whenever the culture medium was replenished, existing patterns would disappear, but they would reemerge as the keratinocytes consumed the nutrients in the medium.
The team also analyzed gene expression within the keratinocytes and found that cell adhesion proteins and proteins related to keratinocyte differentiation were more prominent in areas with high cell density. “Since cell adhesion is crucial for forming regions with high cell density, we specifically looked into the expression of adherens junction (AJ) molecules like E-cadherin and actin,” Natsuga explained. “We discovered that these molecules were concentrated at the intercellular junctions of regions with high density.”
Additionally, the researchers employed a mathematical model to validate that strong cell adhesion leads to the emergence of density patterns under conditions of uniform spatial density and stress. They also demonstrated that the patterns formed by the keratinocytes affected their proliferation and differentiation and that serum starvation impacts epidermal stratification (a specific type of differentiation) in skin cells from mice.
“Our research offers a new and robust model of cell-cell adhesion-induced patterning (CAIP),” Natsuga concluded. “We have enhanced our understanding of the mechanisms behind cellular organization and their implications for cell fate decisions and epithelial stratification.” The team has indicated that epithelial cell-cell adhesion is both essential and sufficient for pattern formation. Their future research will aim to incorporate more variables into the model to explore other concurrent developmental processes.
