Enhancing endogenous regenerative response in mammals by redeploying Cranial Neural Crest Cells pluripotency developmental programs and positional identity remodeling
|Title||Enhancing endogenous regenerative response in mammals by redeploying Cranial Neural Crest Cells pluripotency developmental programs and positional identity remodeling|
|Sponsor||European Research Council - Starting Grant (ERC-StG)|
Associated cell lines
Cell differentiation progresses via a continuous lineage restriction process where cell potential is reduced as the embryo develops. Pluripotent embryonic cells can beget all somatic cell types, but this capacity is rapidly restricted during the formation of the three germ layers, each giving rise to distinct cell types. Uniquely among vertebrates, a stem cell-like population arising in the embryo rostral part – called cranial neural crest cells (CNCC) – challenges this paradigm. CNCC not only give rise to ectoderm derivatives, such as neurons and glia, but also to cell types canonically associated with the mesoderm such as bone and cartilage of the face. I demonstrated that murine CNCC naturally reverse cell differentiation to return into a pluripotent state during development. In addition, I showed pre-migratory CNCC carry positional information reflective of their spatial origin in the neuroepithelium. However, this identity is subsequently erased with migratory CNCC forming a transcriptionally homogenous population, which later re-diversifies as CNCC undergo commitment events. In my research proposal, using single-cell transcriptomics and genomics assays I seek to uncover and characterize gene regulatory networks and chromatin rearrangements regulating the reemergence of pluripotency programs within CNCC and the underlying reprograming of cellular identity. Using established in vitro differentiation protocols to differentiate human ESC into human CNCC will allow us to test if our findings are relevant for human biology. This will greatly increase the significance of the project and help repositioning candidate drugs that could be quickly translated into clinical trials for regenerative medicine.