Signal to Regeneration

forthcoming

"One of the enduring questions in biology is understanding why mammals, unlike amphibians, are unable to regenerate their limbs. Recently, our knowledge of this fascinating and clinically relevant topic has evolved from tissue-level observations in amphibians to comprehensive cellular characterizations. My research was among the first to uncover the cellular composition of regeneration using single-cell RNA sequencing (scRNA-Seq), revealing the critical mechanisms of regenerative epithelial signaling center cell types (Aztekin et al., 2019, 2021). Building on this, my lab has established the equivalence of these cell types across species, including mammals (Zhong et al., 2023). Concurrently, we have developed novel, simplified models to probe their properties in detail (Aztekin et al., 2021; Skoufa et al., 2024). The overarching goal of ""Signal to Regeneration"" (SigReg) is to determine the potential of mammalian regeneration by dissecting the properties of regenerative signaling center cell types. For this, we will employ our mammalian stem cell protocols, skin cultures, and adult mouse amputation models in combination with imaging and sequencing. SigReg will elucidate: (1) how signaling centers quantitatively and dynamically interact with other populations, (2) which environmental factors shape the epigenetic landscape to form regenerative signaling centers in adult mouse skin, and (3) whether grafting signaling center cells can induce regeneration programs following mouse digit amputations. SigReg will establish the quantitative features of signaling centers while demonstrating the critical role of environmental and biomechanical factors in shaping a regenerative histone landscape in adult mice. By applying insights from amphibian studies to mammals, our findings have the potential to pave the way for inducing mammalian digit regeneration, potentially revolutionizing our understanding of regeneration and fueling research and the broader field for decades to come."