Epithelial-to-Mesenchymal Transition in the Female Reproductive Tract: From Normal Functioning to Disease Pathology

Bilyk, Olena; Coatham, Mackenzie; Jewer, Michael; Postovit, Lynne-Marie

doi:10.3389/fonc.2017.00145

Cited by 106 publications

(101 citation statements)

References 247 publications

(336 reference statements)

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“…Furthermore, TGFβ signaling is crucial for the epithelial to mesenchymal transition (EMT), in which cells lose their epithelial characteristics and acquire migratory behavior (28). EMT is necessary for the development and normal functioning of female reproductive organs such as the ovaries and the uterus and dysregulation may cause endometriosis, adenomyosis, and carcinogenesis (29).…”

Section: Discussionmentioning

confidence: 99%

The endometrial transcription landscape of MRKH syndrome

Hentrich

Koch

Weber

et al. 2020

Preprint

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The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. While genetic causes have been identified for a small subset of patients and epigenetic mechanisms presumably contribute to the pathogenic unfolding, too, the etiology of the syndrome has remained largely enigmatic. A comprehensive understanding of gene activity in the context of the disease is crucial to identify etiological components and their potential interplay. So far, this understanding is lacking, primarily due to the scarcity of samples and suitable tissue.In order to close this gap, we profiled endometrial tissue of uterus rudiments in a large cohort of MRKH patients using RNA-seq and thereby provide a genome-wide view on the altered transcription landscape of the MRKH syndrome. Differential and co-expression analyses of the data identified cellular processes and candidate genes that converge on a core network of interconnected regulators that emerge as pivotal for the perturbed expression space. With these results and browsable access to the rich data through an online tool we seek to accelerate research to unravel the underlying biology of this syndrome.

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Section: Discussionmentioning

confidence: 99%

The endometrial transcription landscape of MRKH syndrome

Hentrich

Koch

Weber

et al. 2020

Preprint

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“…(Li, VandenBoom et al 2009, Chang, Chao et al 2011. Low levels of miR-200 in addition to a decrease in e-cadherin results in an increase in vimentin, n-cadherin, twist and snail (Bilyk, Coatham et al 2017). Overexpression of leb-7b suppresses cancer cell growth (Xu, Liu et al 2014, Yu, Feng et al 2015 and therefore, may be one of the mechanisms by which C/EBPδ controls the fallopian tube epithelial cell cycle.…”

Section: C/ebpδ Induces An Emt Regulatory Phenotypementioning

confidence: 99%

C/EBPδ demonstrates a dichotomous role in tumor initiation and promotion of epithelial carcinoma

Sowamber

Chehade

Bitar

et al. 2019

Preprint

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High Grade Serous Ovarian Cancer (HGSC) originates primarily from the fallopian tube epithelia. It is postulated that pre-malignant cells can migrate and implant onto the surface of the ovary. We previously reported that genes differentially expressed in the ovulatory phase can predispose the fallopian tube epithelia to transformation. Since ovulation is frequent, we hypothesize that C/EBPδ, a gene expressed in the luteal phase, can modulate the transformation of p53-mutated fallopian tube epithelial cells. Here, we show significantly decreased expression of C/EBPδ in HGSC compared to normal fallopian tube epithelia. We demonstrate that C/EBPδ, lost early during disease progression, is associated with a mesenchymal phenotype in normal fallopian tube epithelia. However, in a subset of HGSC, C/EBPδ expression is maintained. This pre-malignant subset of cells, that express C/EBPδ, promotes a mesenchymal to epithelial transition and promotes migration in the context of p53 mutation. While C/EBPδ over-expression induces cellular characteristics conducive to an EMT-MET switch, it also behaves as a tumor-suppressor, inhibiting cell cycle progression, indicative of its complex role in the pathogenesis of the disease.

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“…intestine (Tetteh et al 2016), liver, pancreas (Tritschler et al 2017), hair follicles (Merrell and Stanger 2016)) in vivo. Endometrial cells were also reported to be highly plastic (Bilyk et al 2017). Evidences already exist that EMT and MET involved in the menstrual regeneration and embryo implantation in the uterus (Bilyk et al 2017).…”

Section: Our Atlas Highlighted a Emt Program In The Epithelial Subsetmentioning

confidence: 99%

“…Endometrial cells were also reported to be highly plastic (Bilyk et al 2017). Evidences already exist that EMT and MET involved in the menstrual regeneration and embryo implantation in the uterus (Bilyk et al 2017). Subpopulation of MET cells in the regeneration zone that express both epithelial marker cytokeratin and stromal cell marker vimentin was involved in the menstrual endometrial regeneration (Patterson et al 2013).…”

Section: Our Atlas Highlighted a Emt Program In The Epithelial Subsetmentioning

confidence: 99%

“…EMT is also shown to properties of endometrial epithelial stem/progenitor cells (Wu et al 2017), which may explain the in vitro culturing of endometrial epithelial stem/progenitor cells from menstrual shedding debris since 10 years ago (Gargett, Schwab, and Deane 2016). EMT was also involved in the pathogenesis, during which, epithelial cells would lose polarity and acquire motility, migration and proliferation, which would play a role in the evolution of adenomyosis, endometriosis and even cancer when dysregulated or under certain microenvironment (Bilyk et al 2017).…”

Section: Our Atlas Highlighted a Emt Program In The Epithelial Subsetmentioning

confidence: 99%

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Cell atlas of human uterus

Liu

et al. 2018

Preprint

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The human uterus is a highly dynamic tissue that undergoes repeated damage repair and regeneration during the menstrual cycle, which make it ideal model to study tissue regeneration and pathological process. Stem/progenitors were speculated to be involved in the regeneration of endometrial epithelial and pathogenesis of endometriosis. But the identity, microenvironment and regulatory mechanisms of the uterus epithelial stem/progenitors in vivo remain unclear. Here, we dissected the cell heterogeneities of the full-thickness human uterus epithelial cells (11 clusters), stroma cells (6 clusters), endothelial cells (5 clusters), smooth muscle cells (2 clusters), myofibroblasts (2 clusters) and immune cells (6 clusters) from 2735 single cell by single cell RNA-seq. Further analysis identified a unique ciliated epithelial cell cluster showing characteristics of stem/progenitors with properties of epithelial-mesenchymal transition (EMT) that mainly localized in the upper functionalis of the endometrium. Ordering the cell subpopulations along the pseudo-space revealed cell clusters possess cellular states of stress, inflammation and apoptosis in the upper functionalis cellular ecosystem of the endometrium. Connectivity map between the human uterus subpopulations revealed potential inflammatory (cytokines and chemokines) and developmental (WNT, FGF, VEGF) signals within the upper functionalis cellular ecosystem of the endometrium, especially from other epithelial clusters, regulating cell plasticity of the EMT-epithelial clusters. This study reconstructed the heterogeneities, space-specific distribution and connectivity map of human uterus atlas, which would provide insight in the regeneration of uterus endometria and reference for the pathogenesis of uterus.

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Epithelial-to-Mesenchymal Transition in the Female Reproductive Tract: From Normal Functioning to Disease Pathology

Cited by 106 publications

References 247 publications

The endometrial transcription landscape of MRKH syndrome

The endometrial transcription landscape of MRKH syndrome

C/EBPδ demonstrates a dichotomous role in tumor initiation and promotion of epithelial carcinoma

Cell atlas of human uterus

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