Differentiated cells across multiple species and organs can re-enter the cell cycle to aid in injury-induced tissue regeneration by a cellular program called paligenosis. Here, we show that activating transcription factor 3 (ATF3) is induced early during paligenosis in multiple cellular contexts, transcriptionally activating the lysosomal trafficking gene Rab7b. ATF3 and RAB7B are upregulated in gastric and pancreatic digestive-enzyme-secreting cells at the onset of paligenosis Stage 1, when cells massively induce autophagic and lysosomal machinery to dismantle differentiated cell morphological features. Their expression later ebbs before cells enter mitosis during Stage 3. Atf3^–/– mice fail to induce RAB7-positive autophagic and lysosomal vesicles, eventually causing increased death of cells en route to Stage 3. Finally, we observe that ATF3 is expressed in human gastric metaplasia and during paligenotic injury across multiple other organs and species. Thus, our findings indicate ATF3 is an evolutionarily conserved gene orchestrating the early paligenotic autodegradative events that must occur before cells are poised to proliferate and contribute to tissue repair.

中文翻译：

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ATF3 诱导 RAB7 控制 paligenosis（一种保守的细胞可塑性程序）中的自降解

跨多个物种和器官的分化细胞可以重新进入细胞周期，通过称为“异变”的细胞程序帮助损伤诱导的组织再生。在这里，我们发现激活转录因子 3 (ATF3) 在多细胞背景下的异种分化早期被诱导，转录激活溶酶体运输基因Rab7b。在 palogenosis 第一阶段开始时，胃和胰腺消化酶分泌细胞中的 ATF3 和 RAB7B 上调，此时细胞大量诱导自噬和溶酶体机制来破坏分化的细胞形态特征。它们的表达随后在细胞进入第 3 阶段有丝分裂之前减弱。Atf3 ^–/–小鼠无法诱导 RAB7 阳性自噬和溶酶体囊泡，最终导致进入第 3 阶段的细胞死亡增加。最后，我们观察到 ATF3 在人类中表达胃化生以及多个其他器官和物种的异基因损伤期间。因此，我们的研究结果表明，ATF3是一个进化上保守的基因，协调早期的自降解事件，这些事件必须在细胞准备增殖并有助于组织修复之前发生。