To establish and maintain organ structure and function, tissues need to balance stem cell proliferation and differentiation rates and coordinate cell fate with position. Cell density and crowding have been shown to play a critical role in instructing single stem cell fate decisions and movement of differentiating cells upward within the tissue, according to scientists from the Max Planck Institute for Biology of Ageing.
Adult skin epidermis is build of different layers. Stem cells reside in the bottom layer where their task is to produce new cells, which then differentiate and move upward into the more specialized upper layer. This differentiation process involves permanent changes in the cells properties to best suit to serve skin's barrier function. The skin must maintain balanced numbers of stem and differentiated cells, as loss of proper balance would result in aberrant tissue structure and therefore function.
"At the beginning of our study we asked ourselves how the skin cells know where they are and what they are supposed to be doing," explained Yekaterina Miroshnikova, lead author of a paper published in Nature Cell Biology earlier this week, and postdoctoral researcher in the lab of Sara Wickström. The researchers analyzed embryonic mouse tissues and cultured stem cells and found an elegant mechanism based on mechanical guidance.
"We observed that dividing stem cells induced a local crowding effect to the stem cell layer, which deformed the cells in the vicinity of this event. Intriguingly, this compression and deformation triggered the differentiation of the neighboring cell,” added Miroshnikova. The crowded and squeezed cells change their properties, leading to their 'escape' from the local stress in the bottom layer and upward movement. "The fact that cells sense what their neighbors are doing and do the exact opposite provides a very efficient and simple way to maintain tissue size, architecture, and function.”
These results demonstrate how a complex tissue such as the human skin can generate and maintain its structure through very simple principles of self-organization. In the future, the group will continue using a combination of computational modeling and cell biology to uncover how genetic mutations that occur during cancer target stem cell proliferation and mechanics to impair this process.
Image: Skin cells growing in a petri dish (green: cytoskeleton, red: cell-cell junction protein). Image courtesy of MPI f. Biology of Ageing.