Abstract
In order to regenerate tissues successfully, stem cells must detect injuries and restore 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 planarian stem cell responses to different injuries by either 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 to target progenitor and tissue production towards missing tissues. Loss of non-pharyngeal tissues only increases non-pharyngeal progenitors, while pharynx removal selectively triggers division and expansion of pharynx progenitors. By pharmacologically inhibiting either mitosis or activation of the MAP kinase ERK, we identify a narrow window of time during which stem cell division and ERK signaling produces pharynx progenitors necessary for regeneration. These results indicate that planarian stem cells can tailor their output to match the regenerative needs of the animal.
Highlights
When faced with injury or disease, many animals can repair or even replace damaged tissue
These animals had delays in feeding, less severe than those treated for five full days (Figure 5—figure supplement 3C), presumably because animals start recovering after drug washout. Those treated for 0–1 day after pharynx amputation recovered feeding ability at normal rates (Figure 5—figure supplement 3C), illustrating that PD exposure that does not affect the production of pharynx progenitors does not delay regeneration. These results indicate that extracellular signal-regulated kinase (ERK) activity 1–2 days after amputation promotes pharynx regeneration by contributing to the increase in pharynx progenitors 3 days after amputation
These data indicate that ERK signaling is not required for the selective increase in pharynx progenitor division induced by pharynx loss
Summary
When faced with injury or disease, many animals can repair or even replace damaged tissue. Others have shown that stem cells respond indiscriminately to tissue removal, incorporating new cells into tissues regardless of whether they have been damaged, suggesting a non-targeted mode of regeneration (LoCascio et al, 2017) Based on these findings, the authors proposed that stem cells non-selectively increase production of any nearby progenitors, determined by the size and position of a wound, rather than the identity of missing tissues (Figure 1C). Eye regeneration following selective removal is not dependent on stem cell division or ERK signaling, suggesting that different injuries may require distinct regenerative mechanisms. In addition to non-targeted and passive modes of regeneration, stem cell behavior can be altered by the loss of specific tissues, selectively channeling their output towards replacement of missing organs
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