Innate Immune Mechanisms Sensing Oncogenic Events in Stem Cells
During aging, many physiological functions gradually deteriorate, such as wound repair, but Surprisingly, our recent study revealed that the SC number is not significantly reduced in aged skin 15, but becomes functionally exhausted. Based on these findings, the second research direction we have established in my laboratory is to continue employing our in utero microinjection technique to build innovative tools and sophisticated models to investigate questions such as what factors trigger SC exhaustion, how SCs become exhausted, and why SC exhaustion leads to delayed wound repair. Interestingly, while we have found that the skin SCs in young animals are intrinsically wired to adapt to inflammation, repeated and chronic exposure of SCs to low magnitude of inflammation can change the activation potential of genes that are frequently imprinted for inflammatory adaptation. This observation demonstrated that epithelial SCs are similar to immune cells which can be exhausted or desensitized by chronic antigen stimulations 16. Thus, we hypothesize that cellular senescence-induced chronic inflammation could epigenetically rewrite the adaptive circuits of any non-senescent SCs in the skin, which cause “epigenetic scars” and temper the capacity of SCs to sense and adapt to the inflammatory environment in the wound.