scholarly journals BAP1/ASXL complex modulation regulates epithelial-mesenchymal transition during trophoblast differentiation and invasion

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Vicente Perez-Garcia ◽  
Georgia Lea ◽  
Pablo Lopez-Jimenez ◽  
Hanneke Okkenhaug ◽  
Graham J Burton ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Normal Function ◽  
Trophoblast Differentiation ◽  
Human Trophoblast ◽  
Mesenchymal Transition ◽  
Trophoblast Stem Cells ◽  
Endogenous Expression ◽  
Trophoblast Stem

Normal function of the placenta depends on the earliest developmental stages when trophoblast cells differentiate and invade into the endometrium to establish the definitive maternal-fetal interface. Previously, we identified the ubiquitously expressed tumour suppressor BRCA1-associated protein 1 (BAP1) as a central factor of a novel molecular node controlling early mouse placentation. However, functional insights into how BAP1 regulates trophoblast biology are still missing. Using CRISPR/Cas9 knockout and overexpression technology in mouse trophoblast stem cells, here we demonstrate that the downregulation of BAP1 protein is essential to trigger epithelial-mesenchymal transition (EMT) during trophoblast differentiation associated with a gain of invasiveness. Moreover, we show that the function of BAP1 in suppressing EMT progression is dependent on the binding of BAP1 to additional sex comb-like (ASXL1/2) proteins to form the polycomb repressive deubiquitinase (PR-DUB) complex. Finally, both endogenous expression patterns and BAP1 overexpression experiments in human trophoblast stem cells suggest that the molecular function of BAP1 in regulating trophoblast differentiation and EMT progression is conserved in mice and humans. Our results reveal that the physiological modulation of BAP1 determines the invasive properties of the trophoblast, delineating a new role of the BAP1 PR-DUB complex in regulating early placentation.

scholarly journals MAP3K4/CBP-Regulated H2B Acetylation Controls Epithelial-Mesenchymal Transition in Trophoblast Stem Cells

2011 ◽  
Vol 8 (5) ◽  
pp. 525-537 ◽  
Author(s):  
Amy N. Abell ◽  
Nicole Vincent Jordan ◽  
Weichun Huang ◽  
Aleix Prat ◽  
Alicia A. Midland ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

scholarly journals Human trophoblast stem cells: Real or not real?

Placenta ◽  
2017 ◽  
Vol 60 ◽  
pp. S57-S60 ◽  
Author(s):  
Ching-Wen Chang ◽  
Mana M. Parast
Keyword(s):  
Stem Cells ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

scholarly journals Telomeric NAP1L4 and OSBPL5 of the KCNQ1 Cluster, and the DECORIN Gene Are Not Imprinted in Human Trophoblast Stem Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11595 ◽  
Author(s):  
Jennifer M. Frost ◽  
Ramya Udayashankar ◽  
Harry D. Moore ◽  
Gudrun E. Moore
Keyword(s):  
Stem Cells ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

scholarly journals Efficient derivation of human trophoblast stem cells from primed pluripotent stem cells

2021 ◽  
Vol 7 (33) ◽  
pp. eabf4416
Author(s):  
Yanxing Wei ◽  
Tianyu Wang ◽  
Lishi Ma ◽  
Yanqi Zhang ◽  
Yuan Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chromatin Accessibility ◽  
Placental Development ◽  
Differentiation Potential ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Early Placenta ◽  
And Function

Human trophoblast stem cells (hTSCs) provide a valuable model to study placental development and function. While primary hTSCs have been derived from embryos/early placenta, and transdifferentiated hTSCs from naïve human pluripotent stem cells (hPSCs), the generation of hTSCs from primed PSCs is problematic. We report the successful generation of TSCs from primed hPSCs and show that BMP4 substantially enhances this process. TSCs derived from primed hPSCs are similar to blastocyst-derived hTSCs in terms of morphology, proliferation, differentiation potential, and gene expression. We define the chromatin accessibility dynamics and histone modifications (H3K4me3/H3K27me3) that specify hPSC-derived TSCs. Consistent with low density of H3K27me3 in primed hPSC-derived hTSCs, we show that knockout of H3K27 methyltransferases (EZH1/2) increases the efficiency of hTSC derivation from primed hPSCs. Efficient derivation of hTSCs from primed hPSCs provides a simple and powerful model to understand human trophoblast development, including the pathogenesis of trophoblast-related disorders, by generating disease-specific hTSCs.

scholarly journals Super-enhancer-guided mapping of regulatory networks controlling mouse trophoblast stem cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Bum-Kyu Lee ◽  
Yu jin Jang ◽  
Mijeong Kim ◽  
Lucy LeBlanc ◽  
Catherine Rhee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Trophoblast Stem Cells ◽  
Healthy Pregnancy ◽  
Trophoblast Stem ◽  
Super Enhancer ◽  
Transcriptional Regulatory

Abstract Trophectoderm (TE) lineage development is pivotal for proper implantation, placentation, and healthy pregnancy. However, only a few TE-specific transcription factors (TFs) have been systematically characterized, hindering our understanding of the process. To elucidate regulatory mechanisms underlying TE development, here we map super-enhancers (SEs) in trophoblast stem cells (TSCs) as a model. We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated. Mapping targets of 27 SE-predicted TFs reveals a highly intertwined transcriptional regulatory circuitry. Intriguingly, SE-predicted TFs show 4 distinct expression patterns with dynamic alterations of their targets during TSC differentiation. Furthermore, depletion of a subset of TFs results in dysregulation of the markers for specialized cell types in placenta, suggesting a role during TE differentiation. Collectively, we characterize an expanded TE-specific regulatory network, providing a framework for understanding TE lineage development and placentation.

scholarly journals Synthesis and Organization of Hyaluronan and Versican by Embryonic Stem Cells Undergoing Embryoid Body Differentiation

2009 ◽  
Vol 58 (4) ◽  
pp. 345-358 ◽  
Author(s):  
Shreya Shukla ◽  
Rekha Nair ◽  
Marsha W. Rolle ◽  
Kathleen R. Braun ◽  
Christina K. Chan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Embryoid Body ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Proteolytic Fragment ◽  
Mesenchymal Transition ◽  
Hyaluronan Synthases

Embryonic stem cells (ESCs) provide a convenient model to probe the molecular and cellular dynamics of developmental cell morphogenesis. ESC differentiation in vitro via embryoid bodies (EBs) recapitulates many aspects of early stages of development, including the epithelial–mesenchymal transition (EMT) of pluripotent cells into more differentiated progeny. Hyaluronan and versican are important extracellular mediators of EMT processes, yet the temporal expression and spatial distribution of these extracellular matrix (ECM) molecules during EB differentiation remains undefined. Thus, the objective of this study was to evaluate the synthesis and organization of hyaluronan and versican by using murine ESCs during EB differentiation. Hyaluronan and versican (V0 and V1 isoforms), visualized by immunohistochemistry and evaluated biochemically, accumulated within EBs during the course of differentiation. Interestingly, increasing amounts of a 70-kDa proteolytic fragment of versican were also detected over time, along with ADAMTS-1 and −5 protein expression. ESCs expressed each of the hyaluronan synthases (HAS) −1, −2, and −3 and versican splice variants (V0, V1, V2, and V3) throughout EB differentiation, but HAS-2, V0, and V1 were expressed at significantly increased levels at each time point examined. Hyaluronan and versican exhibited overlapping expression patterns within EBs in regions of low cell density, and versican expression was excluded from clusters of epithelial (cytokeratin-positive) cells but was enriched within the vicinity of mesenchymal (N-cadherin-positive) cells. These results indicate that hyaluronan and versican synthesized by ESCs within EB microenviron-ments are associated with EMT processes and furthermore suggest that endogenously produced ECM molecules play a role in ESC differentiation. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

Derivation of human trophoblast stem cells from human pluripotent stem cells

Placenta ◽  
2019 ◽  
Vol 83 ◽  
pp. e59
Author(s):  
Adam Mischler ◽  
Victoria Karakis ◽  
Adriana San Miguel ◽  
Balaji Rao
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem
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