The single-cell transcriptional landscape of the axolotl

Abstract The Mexican axolotl (Ambystoma mexicanum) is a promising tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, during which their regeneration capacity and lifespan gradually decline. However, a system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls is still lacking. Here, we developed a single-cell RNA-seq method based on combinatorial hybridization to generate a tissue-based transcriptomic atlas of the adult axolotl. We performed gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell atlas. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls revealed the heterogeneity of structural cells in different tissues and established their regulatory network. Furthermore, we described dynamic gene expression patterns during limb development in neotenic axolotls. These data serve as a resource to explore the molecular identity of the axolotl as well as its metamorphosis.