长期 EMT 诱导过程中获得的表观遗传记忆控制着向上皮状态的恢复。
Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state.
机构信息
Centre for BioSystems Science and Engineering, Indian Institute of Science, Bengaluru 560012, India.
Department of Biology, Widener University, Chester, PA 19013, USA.
出版信息
J R Soc Interface. 2023 Jan;20(198):20220627. doi: 10.1098/rsif.2022.0627. Epub 2023 Jan 11.
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 TGF need 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-TGF withdrawal. 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'.
上皮-间充质转化（EMT）及其逆转的间充质-上皮转化（MET）在胚胎发育、创伤愈合和癌症转移过程中至关重要。虽然 EMT 诱导过程中的短期表型变化是可逆的，但长期 EMT 诱导通常与不可逆性相关。在这里，我们表明，TGF 诱导 MCF10A 细胞长期 EMT 诱导后出现的表型变化并非不可逆转，而是具有比短期诱导中观察到的更长的可逆转时间尺度。接下来，我们使用一种现象学数学模型来解释 ZEB 家族通过染色质介导的 miR-200 家族的表观遗传沉默，突出了在长期 EMT 诱导过程中获得的表观遗传记忆如何减缓 TGF 去除后向上皮状态的恢复。我们的研究结果表明，表观遗传修饰因子可以控制 EMT 逆转的程度和时间尺度，并建议谨慎对待将长期 EMT 诱导中观察到的表型变化标记为“不可逆”。
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