Principal Investigator Peter Reddien
A cellular explanation for planarian regeneration has been sought since the late 1800s, when a population of proliferative cells (neoblasts) was identified. A key unanswered question has been whether planarian regeneration is explained by a cell type displaying pluripotency (capacity to produce all cell types of the soma) at the single cell level, or by the collective action of multiple dividing cell types that each has limited and different potential. To address this question we developed single cell assays and determined that certain individual cells could divide to clonally generate many similar dividing cells and displayed broad differentiation potential. We named such cells clonogenic neoblasts (cNeoblasts). Single cNeoblasts were able to restore regenerative capacity to lethally irradiated hosts lacking all other cell division, ultimately converting hosts to the genotype of the donor. We conclude that pluripotent stem cells persist into adulthood providing a cellular basis for the remarkable regenerative abilities of planarians.
The hallmark attributes of stem cells are the capacity for self-renewal and the ability to produce one or more differentiated cell types. We aim to understand these stem cell features, as well as the molecular basis of pluripotency, by molecular genetic study of planarian cNeoblasts. Planarians cNeoblasts and their progeny cells are regulated by contextual cues (wounding, growth, homeostatic replacement of aged cells) and are capable of replacing essentially every cell type in the animal. This rich stem cell biology can now be studied with emerging tools: any gene desired can be inhibited and the effects on neoblasts in vivo assessed, we can isolate >100,000 neoblasts in a day by flow cytometry, and assays exist for assessing neoblast differentiation. Together, these attributes and tools present a powerful new approach to stem cell biology.