CORDheal · The roadmap enabling spinal cord regeneration in mammals

It is widely documented that the adult mammalian central nervous system (CNS) does not regenerate. This failure results from the inhibitory scar environment and the decline of developmental growth programs. Overturning this dogma, the PI recently demonstrated that the spiny mouse (Acomys cahirinus) regenerates spontaneously the spinal cord, with robust functional recovery. Her current preliminary data support that an early switch occurs in the injured Acomys spinal cord, allowing scar reversion and activation of a regenerative program. In CORDheal, this exceptional non-model organism will be used to address the knowledge gap on the mechanisms enabling a mammal to regenerate the CNS. The pioneering nature of the PI’s data and her unique combined expertise in CNS regeneration and Acomys biology, places the PI at the forefront of the field. To find the roadmap enabling spinal cord regeneration in mammals, a single cell RNAseq/ATACseq atlas of the injured spinal cord of Acomys and Mus (regeneration-incompetent mouse) will allow discovering cell populations that enable activation of pathways supporting scar avoidance and promoting regeneration. The extent to which regeneration recapitulates development, and the possible birth of novel genes that may contribute to adaptive evolutionary innovation will be tested. As major instructive programs that allow regeneration of different Acomys tissues may be similar, comparative analyses amongst different regenerating Acomys organs will follow. Lastly, to determine when regenerative ability evolved in mammals, other members of the Deomyinae subfamily (to which Acomys belongs) will be assessed for regenerative properties. This will allow finding putative close divergent species, providing ideal conditions to narrow down differences between regeneration and scarring. This ambitious and pioneering program will push current research boundaries to unveil vital cell adaptive mechanisms underlying regeneration in mammals.