Loss of plac8 expression rapidly leads pluripotent stem cells to enter active state during planarian regeneration

The regenerative ability of planarians relies on their adult pluripotent stem cell population. Although all stem cells express a piwi homolog. recently it has become possible to classify the piwi+ stem cell population into specialized subpopulations according to the expression of genes related to differentiation. However, piwi+ stem cells behave practically as a homogeneous population after amputation, during which stem cells show accelerated proliferation, named 'induced hyperproliferation'. Here, we show that plac8-A was expressed in almost all of the stem cells, and that a decrease of the plac8-A expression level led to induced hyperproliferation uniformly in a broad stem cell subpopulation after amputation. This reduction of plac8-A expression was caused by activated JNK signaling after amputation. Pharmacological inhibition of JNK signaling caused failure to induce hyperproliferation and resulted in regenerative defects. Such defects were abrogated by simultaneous knockdown of p/ac8-A expression. Thus, JNK-dependent suppression of plac8-A expression is indispensable for stem cell dynamics involved in regeneration. These findings suggest that plac8-A acts as a molecular switch of piwi+ stem cells for entry into the regenerative state after amputation.

Automated summary

The regenerative ability of planarians relies on their adult pluripotent stem cell population. Recent research has shown that piwi+ stem cells can be classified into specialized subpopulations based on the expression of differentiation-related genes. However, after amputation, piwi+ stem cells behave as a homogenous population and show accelerated proliferation, called 'induced hyperproliferation'. This study reveals that the reduction of plac8-A expression, caused by activated JNK signaling after amputation, is responsible for the induced hyperproliferation in a broad stem cell subpopulation. Inhibition of JNK signaling leads to regenerative defects, which can be rescued by knockdown of plac8-A expression. This suggests that JNK-dependent suppression of plac8-A is crucial for the dynamics of stem cells involved in regeneration and acts as a molecular switch for piwi+ stem cells to enter the regenerative state.