Meeting Abstract
The nervous system is extremely complex, composed of many cell-types creating intricate circuits responsible for coordinating action. Adding to the previously known diversity of cell-types in the nervous system, single-cell RNA sequencing (scRNAseq) in select organisms has uncovered tremendous heterogeneity in neural cell-types. Within these adult organisms, few are capable of regenerating diverse neural cell-types and even fewer are able to regenerate their entire nervous system. Acoel worms represent a major phyletic lineage capable of robust regeneration and include the new research organism, Hofstenia miamia. Hofstenia is capable of whole-body regeneration, i.e. it has the ability to replace any missing cell-type, via differentiation of its adult pluripotent stem cells, called neoblasts. Hofstenia has an organized nervous system and can regenerate all missing neural cells-types and structures, and we sought to identify the molecular/genetic regulators governing the transition from neoblast to differentiated neural cell-type during regeneration. Utilizing scRNAseq data, we identified putative neural populations and subpopulations, which we validated using fluorescent in situ hybridization and immunohistochemistry. Within each major neural population, we recovered candidate transcription factors that we hypothesize to govern differentiation of neural populations during regeneration. We are utilizing systemic RNAi to determine the functions of these transcription factors during regeneration with regards to the replacement of diverse neural cell-types. This work will reveal mechanisms for neural regeneration as well as provide a comparative framework to understand the evolution of these mechanisms.
