Types or States? Cellular Dynamics and Regenerative Potential

Abstract

Many of our organs can maintain and repair themselves during homeostasis and injury, as a result of the action of tissue-specific, multipotent stem cells. However, recent evidence from mammalian systems suggests that injury stimulates dramatic plasticity, or transient changes in cell potential, in both stem cells and more differentiated cells. Planarian flatworms possess abundant stem cells, making them an exceptional model for understanding the cellular behavior underlying homeostasis and regeneration. Recent discoveries of cell lineages and regeneration-specific events provide an initial framework for unraveling the complex cellular contributions to regeneration. In this review, we discuss the concept of cellular plasticity in the context of planarian regeneration, and consider the possibility that pluripotency may be a transient, probabilistic state exhibited by stem cells.

Keywords: Planaria; homeostasis; plasticity; regeneration; stem cells.

Figure 1

Planarian anatomy. (A) Various organs in asexual flatworms. Each organ illustrated here consists of several cell types. (B) Left, live animal extending its pharynx. Right, pharynx anatomy in isolated pharynges with stained epithelial cells, muscle, neurons (α-FMRF-amide). Scale bars, 100μm.

Figure 2

Lineage progenitors for organ regeneration. (A) Several specialized progenitors for many tissues are produced during homeostasis, derived from pluripotent stem cells. (B) Changing distribution of organ-specific progenitor markers after amputations (highlighted in pink or purple).

Figure 3

Amputation initiates polarity re-establishment. Removal of anterior and posterior regions induces dramatic changes in the animal. Transcriptional markers of the anterior and posterior (represented by blue and red, respectively) are expressed in differentiated cells, and removed after significant amputations, leaving disproportional axial patterning in fragments. Within 12–24 hours, expression of these markers is reestablished in fragments and instructs fate determination of regenerating tissues.

Figure 4

Two models for progenitor dynamics during homeostasis and regeneration. In the deterministic model, stem cells produce specialized progenitors that statically express specific fate markers. Injury stimulates changes in the rates and types of progenitors produced, allowing animals to respond to different wounds. In the probabilistic model, stem cells and their progenitors transiently express fate markers (RNA concentration represented by curves, with colors representing different genes being expressed at different times). Wounding may alter the frequency and/or persistence of expression of fate determinants, thus producing the necessary cell types required for regeneration.