Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state

被引：16

作者：

Jain, Paras ^{[1
]}

Corbo, Sophia ^{[2
]}

Mohammad, Kulsoom ^{[2
]}

Sahoo, Sarthak ^{[1
]}

Ranganathan, Santhalakshmi ^{[3
]}

George, Jason T. ^{[4
]}

Levine, Herbert ^{[5
,6
,7
]}

Taube, Joseph ^{[3
]}

Toneff, Michael ^{[2
]}

Jolly, Mohit Kumar ^{[1
]}

机构：

[1] Indian Inst Sci, Ctr Biosyst Sci & Engn, Bengaluru 560012, India

[2] Widener Univ, Dept Biol, Chester, PA 19013 USA

[3] Baylor Univ, Dept Biol, Waco, TX 76706 USA

[4] Texas A&M Univ, Dept Biomed Engn, College Stn, TX 76798 USA

[5] Northeastern Univ, Ctr Theoret Biol Phys, Boston, MA 02115 USA

[6] Northeastern Univ, Dept Phys, Boston, MA 02115 USA

[7] Northeastern Univ, Dept Bioengn, Boston, MA 02115 USA

来源：

JOURNAL OF THE ROYAL SOCIETY INTERFACE | 2023年 / 20卷 / 198期

关键词：

epithelial-mesenchymal plasticity; mathematical modelling; chromatin-mediated epigenetic regulation; mesenchymal-epithelial transition (MET); epigenetic memory; CELLULAR DECISION-MAKING; MESENCHYMAL PLASTICITY; DNA METHYLATION; PROMOTES EMT; TRANSITION; DYNAMICS; ZEB1; VARIABILITY; REPRESSION; STABILITY;

D O I：

10.1098/rsif.2022.0627

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta 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 beta 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'.

引用

页数：17

共 70 条

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