Single-cell analyses of axolotl forebrain organization, neurogenesis, and regeneration

Preprint: https://doi.org/10.1101/2022.03.21.485045 Abstract: Salamanders are important tetrapod models to study brain organization and regeneration, however the identity and evolutionary conservation of brain cell types is largely unknown. Here, we delineate cell populations in the axolotl telencephalon during homeostasis and regeneration, representing the first single-cell genomic and spatial profiling of an anamniote tetrapod brain. We identify glutamatergic neurons with similarities to amniote neurons of hippocampus, dorsal and lateral cortex, and conserved GABAergic neuron classes. We infer transcriptional dynamics and gene regulatory relationships of postembryonic, region-specific direct and indirect neurogenesis, and unravel conserved signatures. Following brain injury, ependymoglia activate an injury-specific state before reestablishing lost neuron populations and axonal connections. Together, our analyses yield key insights into the organization, evolution, and regeneration of a tetrapod nervous system. File description: all_nuclei_clustered_highlevel_anno.rds - Seurat object including all snRNA-seq data from uninjured pallium, both from microdissections and whole pallium multiome. pallium_metadata_simp.csv - csv file containing a simplified version of the metadata for the uninjured pallium Edu_1_2_4_6_8_12_fil_highvarfeat.rds - Seurat object containing all Div-seq data for the pallium injury time course divseq_predicted_metadata.csv - csv file containing a simplified version of the metadata for the pallium injury time course ep_wpi_srat.rds - Seurat object containing an integrated version of ependymoglia cells from uninjured and injured pallium (see Fig 6 in the preprint). D1_113_sub_b.rds - Seurat object containing a Visium data for the axolotl pallium multiome_integATAC_SCT.rds - Signac object containing the data used for multiome analysis of the uninjured whole pallium predictions_cell2loc.csv - csv file containing cell2location scores for the uninjured pallium cell types in the Visium dataset