RNA-Seq of WT and Mecp2 KO cerebellum after transplantation with Neural/Precursor Cells (NPCs)

RTT represents the first genetic cause of severe intellectual disability in girls and although potentially treatable, no cure is currently available. The identification of a valid therapy is delayed by the need of maintaining physiological MeCP2 levels and by the limited comprehension of its roles. Neural precursor cell (NPC) transplantation has already been proved safe and efficacious in many neurological disorders. Particularly, in neurodegenerative conditions, their mechanism of action mainly relies on cell replacement; however, when neurodegeneration is absent, it has been demonstrated that NPCs act by a so-called “bystander” mechanism, by releasing of a plethora of molecules, including inflammatory cytokines, chemokines, trophic factors and stem cell regulators. These factors exert immunomodulatory and neuroprotective effects, and can also modulate synaptic plasticity. Willing to come with a novel cure for RTT, starting from our data indicating the therapeutic potential of NPCs in Mecp2 deficient animals and neurons, we aim at identifying the molecules and/or pathways involved in their therapeutic benefit, a required step for moving the therapy from the bench to the bedside. By bulk RNA sequencing (RNA-seq), we analyzed the transcriptional profile of the cerebellum derived from WT and Mecp2 KO animals, injected with NPCs or vehicle (PBS) at post-natal day (P) 45. Analysis was conducted 20 days after transplantation (at P60). n=5-6 animals/exp.group.