The Queen is Dead: Understanding Stem Cell Hierarchies using Freshwater Planarians

The freshwater planarian (flatworm) has been used by biologists for over 100 years to study regeneration, however, over the past decade it is re-emerging as a powerful model for stem cell biology. Here we explore the molecular mechanisms by which planarians control their pluripotent adult stem cells in order to replace specific numbers and types of differentiated daughter cells. We apply both whole-organism and single cell RNA-sequencing and find that an RNA-binding protein, MEX3, is involved in the critical decision on whether a cell remains a stem cell, or differentiates. From this, we have pieced together the cellular hierarchy from stem cell to epithelial cell, and find that it is relatively shallow, with no master stem cell type (“Queen”) at the top.