Planarian stem cells sense the identity of missing tissues to launch targeted regeneration

Abstract

In order to regenerate tissues successfully, stem cells must first detect injuries and then produce missing cell types through largely unknown mechanisms. Planarian flatworms have an extensive stem cell population responsible for regenerating any organ after amputation. Here, we compare stem cell responses to different injuries by amputation of a single organ, the pharynx, or removal of tissues from other organs by decapitation. We find that planarian stem cells adopt distinct behaviors depending on what tissue is missing: loss of non-pharyngeal tissues increases numbers of non-pharyngeal progenitors, while removal of the pharynx specifically triggers proliferation and expansion of pharynx progenitors. By pharmacologically inhibiting either proliferation or activation of the MAP kinase ERK, we identify a narrow window of time during which proliferation, followed by ERK signaling, produces pharynx progenitors necessary for regeneration. Further, unlike pharynx regeneration, eye regeneration does not depend on proliferation or ERK activation. These results indicate that stem cells tailor their proliferation and expansion to match the regenerative needs of the animal.

Formation and Spontaneous Long-Term Repatterning of Headless Planarian Flatworms

“…In the highly regenerative planarian flatworm, ERK phosphorylation is one of the first responses to injury, detectable 15 min after cutting 7 . ERK signaling has been argued to be important in planaria for overall regeneration 7 , to play a role in allowing differentiation 6 , to activate stem cell subpopulations 8 and to play a headspecific role 9 . Several studies have shown that ERK inhibition immediately following amputation leads to the formation of headless animals 6,7,9 .…”