Exploring transcriptional single-cell signatures in a mouse model of epilepsy caused by a polyalanine expansion mutation in Aristaless-related homeobox gene.

The X-linked Aristaless-related homeobox gene (ARX) encodes an interneuron-specific transcription factor (TF) with a key role in mammalian corticogenesis and GABAergic sub-type specification. Elongations in two of its four polyalanine (PolyA) tracts have been found in incurable neurodevelopmental disorders (NDDs), such as intellectual disability (XLID) and infantile spasms, a catastrophic chronic epilepsy resistant to standard cures. Our main objective is to disclose cell-to-cell expression variability, in terms of transcriptomic dynamics, underlying cellular heterogeneity and cell populations that bulk the Arx polyA epileptic brain. Understanding all these aspects may help us to identify cell-specific epileptic-biomarkers linked to the disease-response that could be used as druggable molecules in anti-epileptic drug discovery research.