Control of cell differentiation potential is essential to embryo development and homeostasis maintenance. Pluripotent embryonic cells can beget all somatic cell types, but this capacity is rapidly restricted during the formation of the three germ layers – endoderm, mesoderm and ectoderm – each giving rise to distinct cell lineages. Uniquely among vertebrates, a stem cell-like population arising in the embryo rostral part – called cranial neural crest cells – challenges this paradigm. Cranial neural crest cells 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 during development, murine cranial neural crest cells naturally re-express pluripotency factors to reverse cell differentiation and return into a higher pluripotency state, resulting in the expansion of their differentiation potential. Furthermore, they maintain a high level of plasticity throughout development and rapidly reset their molecular positional identity to adapt to future locations in the embryo.
By combining state-of-the-art single-cell multi-omics screens, functional assays in vivo and in vitro and tissue repair studies, my laboratory seeks to uncover and comprehend gene regulatory networks and chromatin rearrangements regulating the reemergence of pluripotency programs and the underlying reprograming of cellular identity during development and regeneration. The interdisciplinary scope of experimental strategies will help understand how these fundamental processes are regulated and might result in novel strategies to stimulate endogenous regeneration and ameliorate craniofacial tissue repair.