Homeostasis

 
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Tissue regeneration is the process by which our bodies maintain normal tissue function. Specifically, tissue regeneration is an extremely dynamic process, requiring coordination of many cellular behaviors such as self-renewal and differentiation.

In order to understand how each cell decision impacts surrounding cells we are using light-activated fluorophores that allow us to distinctly mark and track any cell of choice to provide a history of their behaviors over time (Figure 1). Close monitoring of these cells and their neighbors as well as long time-lapse recordings are elucidating the consequences of each individual cell decision for its immediate neighbors at the level of a tissue (Figure 2).

Figure 1

Figure 1

Figure 2

Figure 2

These approaches have allowed us to begin to understand what factors dictate stem cell behavior, including: 1) that location dictates stem cell fate (Rompolas, Nature 2013), 2) that that stem cell decisions are balanced through extrinsic regulation via TGFβ signaling from the niche (Mesa 2015), 3) that β-catenin activation induces stem cell autonomous survival as well as non-autonomous growth of neighboring stem cells (Mesa 2015; Deschene*, Myung* 2014), and 4) that epidermal stem cells are equipotent for self-renewal and differentiation behaviors (Rompolas*, Mesa* 2016).

However, we still lack answers about how stem cells integrate the cellular and molecular inputs from the multitude of cells that surround them to execute a proper homeostatic program.

Since stem cells are often direct neighbors, can their behaviors or cell fate decisions influence those of the stem cells around them? What molecular mechanisms allow stem cells to remain highly plastic and able to respond to changing demands from the tissue? And what roles do other closely apposed distinct cell types have in controlling stem cell behavior?