Stem Cells in Organ Regeneration
Every day our body makes and loses billions of cells. This continuous regeneration is sustained by stem cells, which act as a lifelong reservoir by self-renewing and differentiating into the different lineages of a tissue.
In the Greco lab, our goal is to define how tissues maintain themselves throughout the course of our lives in the face of continuous cellular turnover, frequent injuries, and spontaneous mutations.
Despite the highly dynamic nature of this process, the field has been limited by the inability to track the same cells over time and interrogate their behaviors in a live mammal. To overcome this challenge, we took inspiration from the developmental biology field to develop novel tools that integrate imaging of stem cells in their niche in live mice with genetics and cell biological approaches. This allows us to understand the complex orchestration of tissue regeneration using the skin as model system.
Our novel live imaging approach (Rompolas 2012) to track and manipulate stem cells in live animals has enabled us to explore multiple fundamental principles of tissue biology:
The importance of support. We discovered that stem cells can be replaced, but loss of the niche disables tissue regeneration. We identified extrinsic cues that spatially organize different stem cell behaviors, including survival and death.
Flexibility to demands. We showed that stem cells adapt their fate choices to satisfy tissue requirements after injury and during homeostasis. This adaptability maintains normal tissue architecture, despite mutant cells or aberrant differentiation cues. We also found that stem cell neighbors coordinate their fate choices: differentiation of a stem cell induces symmetrical division of a neighboring stem cell.
Endogenous mechanisms of preventing disease. We demonstrated that the epithelium and mesenchyme possess diverse mechanisms to correct aberrant growths induced by mutational or non-mutational insults, suggesting an exciting concept: that our tissues have innate mechanisms to eliminate tumors in their earliest stages.
These breakthroughs advance our long-term goal of understanding organ homeostasis, injury response, and oncogenic tolerance. On-going projects are looking at understanding the mechanism of skin tolerance to mutations as well as how the different tissue types such as epithelium, fibroblasts, and vasculature contribute to skin homeostasis throughout our lifetimes.