Basic molecular mechanisms that orchestrate stem cell maintenance and fate are widely conserved across kingdoms, allowing for cross-species studies from simple model systems to mammals. In this context, planarians offer extraordinary possibilities containing a reservoir of experimentally accessible adult pluripotent stem cells, “the neoblasts”. Indeed, in vivo reverse genetic manipulation of crucial neoblast regulators allows a fine study of adult stem cell fate in their natural environment. Recent extensive transcriptomics analysis revealed that planarian neoblasts are a widely heterogeneous population including clonogenic and lineage-committed stem cells, constituting a dynamic compartment that talks with differentiated tissue for proper physiological homeostasis and tissue regeneration. In this chapter, we review, in a chronological perspective, the most recent findings in the comprehension of neoblast biology, including their embryonic origin, and compare the most accredited models of pluripotency maintenance and fate determination.
