Molecular and cellular characterization of planarian stem cell microenvironments

Stem cell niches are essential for regulating stem cell self-renewal and differentiation during tissue repair and regeneration. However, the mechanisms supporting stem cell function in highly regenerative organisms, such as the freshwater planarian Schmidtea mediterranea, remain unclear. Using spatial transcriptomics, we identified two cell types associated with planarian stem cells: secretory cells we term "hecatonoblasts" and intestinal cells. Surprisingly, while hecatonoblasts were in close physical proximity to stem cells in the mesenchyme, they were dispensable for regeneration. In contrast, intestinal cells, despite lacking direct contact with stem cells, regulated both their position and function during regeneration. Electron microscopy revealed diverse architectures and cellular composition of stem cell microenvironments, as well as a near absence of junctions between stem and differentiated cells. Our findings demonstrate that planarian stem cells may be regulated by a diverse collection of dynamic microenvironments that collectively support stem cell potency, differentiation, and regenerative capacity.