Stem cell systems and regeneration in planaria

Abstract

Planarians are members of the Platyhelminthes (flatworms). These animals have evolved a remarkable stem cell system. A single pluripotent adult stem cell type ("neoblast") gives rise to the entire range of cell types and organs in the planarian body plan, including a brain, digestive-, excretory-, sensory- and reproductive systems. Neoblasts are abundantly present throughout the mesenchyme and divide continuously. The resulting stream of progenitors and turnover of differentiated cells drive the rapid self-renewal of the entire animal within a matter of weeks. Planarians grow and literally de-grow ("shrink") by the food supply-dependent adjustment of organismal turnover rates, scaling body plan proportions over as much as a 50-fold size range. Their dynamic body architecture further allows astonishing regenerative abilities, including the regeneration of complete and perfectly proportioned animals even from tiny tissue remnants. Planarians as an experimental system, therefore, provide unique opportunities for addressing a spectrum of current problems in stem cell research, including the evolutionary conservation of pluripotency, the dynamic organization of differentiation lineages and the mechanisms underlying organismal stem cell homeostasis. The first part of this review focuses on the molecular biology of neoblasts as pluripotent stem cells. The second part examines the fascinating mechanistic and conceptual challenges posed by a stem cell system that epitomizes a universal design principle of biological systems: the dynamic steady state.

Fig. 1

Examples of European planarian species. From left to right: Polycelis sp., Planaria torva (recently fed), Dendrocoelum lacteum, Schmidtea polychroa, Dugesia gonocephala (recently fed), Schmidtea mediterranea

Fig. 2

Organization of the planarian stem cell system. a Top: stem cell distribution as visualized by whole mount in situ hybridization with the neoblast marker smedwi-1. The image is a maximum intensity projection spanning the D/V axis (anterior is to the right). The stem cell devoid pharynx occupies the dark central area. Scale bar: 200 μm. Bottom: cartoon illustration of the stem cell distribution in a transverse section at the level of the pharynx. Stem cells (red), Ep epithelium, Bm basement membrane, Phx pharynx, VNC ventral nerve cords, Gut lateral branch of the gastrovascular system. b Magnified head region. smedwi-1 RNA expressing Neoblasts (red) are largely absent from the area in front of the photoreceptors (asterisks), but SMEDWI-1 protein persists in anteriorly migrating stem cell progeny (green, antibody staining). Scale bar: 200 μm. c Only smedwi-1 RNA expressing cells (red) divide (blue, H3P antibody staining). Scale bar: 25 μm

Fig. 3

Concepts in stem cell lineage organization. a “Differentiation on demand”: signals from differentiated cells instruct the fate choice of a pluripotent progenitor. b Stochastic differentiation. Purely cell-intrinsic mechanisms determine the fate choice of a pluripotent progenitor. Tissue loss due to injury (red line symbolizing amputation plane) could affect fate choices in a, but not in b. c Hypothetical differentiation hierarchy utilizing a combination of mechanisms. Initial lineage segregation occurs via cell intrinsic mechanisms (top). Terminal cell fates arise from additional choice points within lineages, involving a combination of (1) local “differentiation on demand” signals in the tissue environment (bottom left); (2) global patterning signals (centre) and (3) self-assembly of complex structures by means of spatiotemporal interactions amongst progenitors. Note that the scheme does not distinguish neoblasts and postmitotic progeny: initial lineage segregation (top) amongst postmitotic progeny would imply uniform neoblast pluripotency; lineage segregation already within dividing cells would imply neoblast heterogeneity in form of transit amplifying cells