The spinal cord is composed of a large diversity of neuron types that are generated during development from a heterogeneous pool of progenitors organized in dorsoventral domains. Each domain is defined by the expression of a particular combination of transcription factors that determine the neuron subtype produced by the progenitors in that domain. Once development is complete, progenitors differentiate or shut down neurogenic programs to convert to adult neural stem cells, when they cease to produce neurons. We have previously described that adult neural stem cells, although purely gliogenic in vivo, retain neurogenic capacity in vitro. This suggests that some neurogenic potential remains and that it may be elicited if the right neurogenic programs are reactivated.
Here we plan to first identify the gene regulatory networks that drive neurogenesis using single cell RNA and ATAC sequencing.
We will perform single cell RNA-seq dataset from e9.5-13.5 developing spinal cord. We will complement it by performing single cell chromatin accessibility (ATAC) sequencing at matching time points. Domain- and neuron subtype-specific molecular trajectories will be annotated and reconstructed guided by Delile et al.. In parallel, developmental data will be integrated with our previously generated single cell RNA and ATAC sequencing from adult neural stem cells in homeostasis and after injury. Integrative analyses will allow us to delineate the neurogenic networks that have been silenced as embryonic progenitors converted to adult neural stem cells and that these cells fail to naturally reactivate during their injury response.