Pattern formation in epithelial cells, particularly in keratinocytes, has long been studied but the exact mechanisms behind this phenomenon remain elusive. A team of researchers from Hokkaido University, led by Associate Professor Ken Natsuga, aimed to shed light on this process by focusing on the role of cell-cell adhesion in governing pattern formation. Using an immortalized keratinocyte cell line called HaCaT, the researchers observed that patterns emerged spontaneously in cultures as cells formed high- and low-density regions. Interestingly, the team found that these patterns were heavily influenced by starvation, with patterns disappearing and reappearing as nutrients in the culture medium were consumed.
Gene expression analysis of the keratinocytes revealed that cell adhesion proteins and differentiation proteins were upregulated in high-density regions, indicating a link between cell adhesion and pattern formation. Specifically, the team found that molecules involved in cell adhesion, such as E-cadherin and actin, were localized at intercellular junctions in high-density regions. Through the use of a mathematical model, the researchers confirmed that strong cell adhesion leads to the formation of density patterns under spatially uniform density and stress conditions. The patterns observed in keratinocytes were also shown to influence cell proliferation and differentiation.
Furthermore, the team demonstrated that serum starvation influences epidermal stratification in skin cells from mice, indicating the broader implications of their findings on cell fate decisions and epithelial stratification. The researchers proposed a novel model of cell-cell adhesion-induced patterning (CAIP), emphasizing the essential role of epithelial cell-cell adhesion in patterning. Future research efforts will focus on incorporating additional variables into the model to gain a deeper understanding of the complex processes that occur during development.
The study conducted by the Hokkaido University researchers provides valuable insights into the mechanisms underlying pattern formation in keratinocytes and epithelial cells. By unraveling the role of cell-cell adhesion in governing pattern formation, the researchers have highlighted the importance of this process in regulating cell proliferation, differentiation, and epithelial organization. Their findings offer a novel perspective on cellular organization and its implications for tissue development, with potential applications in understanding various biological processes.
The team’s use of a mathematical model to confirm the link between strong cell adhesion and density patterns further strengthens their observations and provides a quantitative framework for understanding the underlying mechanisms at play. By focusing on the impact of factors like starvation on pattern formation, the researchers have revealed the dynamic nature of epithelial cell organization and the intricate interactions that drive cellular patterning. Their findings have important implications for future research in the field of developmental biology and tissue engineering.
Overall, the research conducted by the Hokkaido University team represents a significant contribution to the understanding of pattern formation in keratinocytes and epithelial cells. By elucidating the role of cell-cell adhesion in driving pattern formation, the researchers have provided a new perspective on the processes that govern cell organization and fate decisions. Their novel model of cell-cell adhesion-induced patterning lays the foundation for further investigations into the complex mechanisms that underlie epithelial patterning and tissue development.