Loss of plac8 expression rapidly leads pluripotent stem cells to enter active state during planarian regeneration
Loss of plac8 expression rapidly leads pluripotent stem cells to enter active state during planarian regeneration
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DOI：
10.1242/dev.199449
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发表时间：
2022-02-01
期刊：
影响因子：
4.6
通讯作者：
Shibata, Norito
中科院分区：
文献类型：
--
作者：
Lee, Hayoung;Hikasa, Kanon;Shibata, Norito
真涡虫的再生能力依赖于其成体多能干细胞群。尽管所有的干细胞都表达一种piwi同源物。最近，根据与分化相关的基因的表达将Piwi+干细胞群分类为特化亚群成为可能。然而，piwi+干细胞在截肢后实际上表现为同质群体，在此期间干细胞显示加速增殖，称为“诱导过度增殖”。在这里，我们表明，plac 8-A在几乎所有的干细胞中表达，并且plac 8-A表达水平的降低导致截肢后在广泛的干细胞亚群中均匀地诱导过度增殖。这种plac 8-A表达的减少是由截肢后激活的JNK信号转导引起的。JNK信号传导的药理学抑制导致不能诱导过度增殖并导致再生缺陷。通过同时敲低p/ac 8-A表达来消除这种缺陷。因此，JNK依赖性抑制plac 8-A表达是干细胞再生动力学所必需的。这些发现表明，plac 8-A充当piwi+干细胞在截肢后进入再生状态的分子开关。
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.