Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state.
Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state.
复制标题
在长期 EMT 诱导过程中获得的表观遗传记忆控制着上皮状态的恢复。
DOI：
10.1098/rsif.2022.0627
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Jolly,MohitKumar
中科院分区：
文献类型：
--
作者：
Jain,Paras;Corbo,Sophia;Mohammad,Kulsoom;Sahoo,Sarthak;Ranganathan,Santhalakshmi;George,JasonT;Levine,Herbert;Taube,Joseph;Toneff,Michael;Jolly,MohitKumar
上皮-间充质转化(EMT)及其逆间充质-上皮转化(MET)在胚胎发育、伤口愈合和肿瘤转移过程中起着至关重要的作用。虽然短期EMT诱导期间的表型变化是可逆的，但长期EMT诱导通常与不可逆性相关。在这里，我们表明，在转化生长因子β长期诱导的MCF10A细胞中，表型变化不一定是不可逆转的，但与短期诱导相比，具有相对较长的可逆性时间尺度。接下来，使用现象学数学模型来解释染色质介导的ZeB家族对miR-200家族的表观遗传沉默，我们强调了在长期内胚层转化诱导过程中获得的表观遗传记忆是如何减缓转化生长因子β退出后恢复到上皮状态的。我们的结果表明，表观遗传修饰物可以控制EMT可逆性的程度和时间范围，并建议注意不要将长期EMT诱导中看到的表型变化标记为“不可逆”。
Epithelial–mesenchymal transition (EMT) and its reverse mesenchymal–epithelial transition (MET) are critical during embryonic development, wound healing and cancer metastasis. While phenotypic changes during short-term EMT induction are reversible, long-term EMT induction has been often associated with irreversibility. Here, we show that phenotypic changes seen in MCF10A cells upon long-term EMT induction by TGFβneed not be irreversible, but have relatively longer time scales of reversibility than those seen in short-term induction. Next, using a phenomenological mathematical model to account for the chromatin-mediated epigenetic silencing of the miR-200 family by ZEB family, we highlight how the epigenetic memory gained during long-term EMT induction can slow the recovery to the epithelial state post-TGFβwithdrawal. Our results suggest that epigenetic modifiers can govern the extent and time scale of EMT reversibility and advise caution against labelling phenotypic changes seen in long-term EMT induction as ‘irreversible’.