The mammalian central nervous system lacks the capacity to efficiently repair
damaged tissue and restore its original function. Spinal cord injury is a devastating condition associated with lifelong functional impairment and for which there is no curative treatment. An insult to the spinal cord leads to loss of neurons and their connectivity, demyelination, reactive gliosis, inflammation, and formation of a fibrotic scar, which underlie the persistent loss of sensorimotor function. Multiple resident cell types reprogram their homeostatic transcriptional state to contribute to the injury milieu. The transcriptional changes underlying the multicellular response to injury are driven by activation of a wide range of DNA regulatory elements, which encode information for precise spatiotemporal control of gene expression. Enhancer usage is highly diverse and allows us to discriminate among specific cell subtypes and even cell states, to unequivocally identify stimulus-responsive cells. This study aims at providing a comprehensive characterization of the molecular and cellular responses to injury using temporally resolved, single-cell genomic technologies. We, further, intend to learn how usage of DNA regulatory elements is linked to activation of injury-induced transcriptional programs. To this end, we aim to produce a large multiomic map sampling spinal cells at different times after thoracic injury and profiling transcriptional and chromatin accessibility states, simultaneously. With this, we wish to study, by means of cGAN models, how different cells react to injury and how their recruitment evolves over time. Furthermore, we will focus on the discovery of cell type-specific and injury-responsive enhancers that can be linked to the activation of inflammatory and reactive gene expression programs in different cell types. Harnessing this extraordinary diversity in the recruitment of DNA regulatory elements will ultimately allow us to develop more precise strategies for identifying and targeting pathological cell states to promote tissue repair.