MAP3K4 Controls the Chromatin Modifier HDAC6 during Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition

Mobley, Robert J.; Raghu, Deepthi; Duke, Lauren D.; Abell-Hart, Kayley; Zawistowski, Jon S.; Lutz, Kyla; Gomez, Shawn M.; Roy, Sujoy; Homayouni, Ramin; Johnson, Gary L.; Abell, Amy N.

doi:10.1016/j.celrep.2017.02.030

Cited by 54 publications

(58 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the outgrowth assay, abnormal TGC development was evaluated with a TGC marker (Tfap2c), the total areas of outgrowth, and the ICM/TE ratio. Taken together, our findings support the importance of TJs and critical functional roles for trophoblast and further development (DaSilva‐Arnold, Zamudio, Al‐Khan, & Illsley, ; Mobley et al, ; Sivasubramaniyam et al, ).…”

Section: Discussionsupporting

confidence: 84%

See 1 more Smart Citation

The Cxadr–Adam10 complex plays pivotal roles in tight junction integrity and early trophoblast development in mice

Jeong

Ock

Yoo

et al. 2019

Molecular Reproduction Devel

View full text Add to dashboard Cite

Understanding preimplantation embryo development has important implications for assisted reproductive technologies (ARTs) after the introduction of in vitro fertilisation and embryo transfer because most embryonic losses occur during pre/peri‐implantation. Recent studies have shown that tight junctions (TJs) are important components for embryos to develop to the blastocyst stage. However, their biological function after cavitation has not been extensively studied. We examined TJ assembly focusing on coxsackievirus and adenovirus receptor (Cxadr) and A disintegrin and metalloproteinase 10 (Adam10) using siRNA and/or an Adam10‐specific inhibitor (GI254023X). TJ‐associated genes, including occludin and tight junction protein 1 (Tjp1), were downregulated in the Cxadr knockdown (KD) embryos but were unaltered in Adam10 KD embryos. However, Adam10 KD or chemical inhibition affected subcellular localisation of Adam10, Cxadr, and Tjp1, leading to disrupted TJ assembly. Furthermore, Cxadr KD or GI254023X‐treated blastocysts showed a relatively smaller outgrowth area and aberrant expression of transcription factor AP‐2γ, a trophoblast‐specific marker in the in vitro embryo outgrowth assay. In summary, we demonstrated that the Cxadr–Adam10 complex might moderate TJ integrity/stability and play pivotal roles during early embryonic development. Collectively, understanding the establishment of the TJ complex and its integrity will provide insight into translational research for predicting and selecting developmental competency for ART.

show abstract

Section: Discussionsupporting

confidence: 84%

“…Moreover, recent studies have demonstrated the TJ regulatory mechanism during the epithelial to mesenchymal transition and the importance of trophectoderm differentiation via TJs (Calder, Edwards, Betts, & Watson, 2017;Davies et al, 2016;Mobley et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

The Cxadr–Adam10 complex plays pivotal roles in tight junction integrity and early trophoblast development in mice

Jeong

Ock

Yoo

et al. 2019

Molecular Reproduction Devel

View full text Add to dashboard Cite

show abstract

“…Taken together, our findings support the importance of tight junction and critical functional roles for trophoblast development and further development (Sivasubramaniyam et al, 2013;DaSilva-Arnold et al, 2016;Mobley et al, 2017).…”

Section: Resultssupporting

confidence: 78%

Tight Junction Assembly Ensures Maintenance of Pregnancy during Embryogenesis in a Mouse Model

Jeong

Choi

2019

J Anim Reprod Biotechnol

View full text Add to dashboard Cite

Recent studies showed that tight junctions (TJs) integrity and assembly are required for blastocyst development in mouse and pig models. However, the biological functions of TJs associated with embryo implantation and maintenance of pregnancy were not investigated yet. To examine whether disrupted TJs affect further embryo development, we employed RNAi approach and inhibitor treatment. The embryos were injected with Cxadr (Coxsackievirus and adenovirus receptor) siRNA for knock down (KD) and treated with Adam10 (A Disintegrin and Metalloproteinase specific inhibitor 10; GI254023X; SI). We compared blastocyst development and paracellular sealing assay using FITC dextran uptake between control and KD or SI embryos. Finally, we transferred control and Cxadr KD or Adam 10 SI treated blastocyst to uteri of recipients. Cxadr KD and Adam 10 SI showed lower blastocyst development and more permeable to FITC-dextran. Moreover, we observed that half of KD and inhibited embryos failed to maintain pregnancies after the second trimester. Our findings suggested that TJs integrity is required for the maintenance of pregnancy and can be used as a selective marker for the successful application of assisted reproduction technologies.

show abstract

“…We have previously demonstrated that MAP3K4 inhibits HDAC6 expression and activity ( Mobley et al, 2017 ). HDAC6 induces EMT in TS cells by binding to the promoters of epithelial maintenance genes, deacetylating histone H2BK5, and repressing gene expression.…”

Section: Resultsmentioning

confidence: 99%

GALNT3 Maintains the Epithelial State in Trophoblast Stem Cells

et al. 2019

Self Cite

View full text Add to dashboard Cite

SUMMARY O-GalNAc glycosylation is initiated in the Golgi by glycosyltransferases called GALNTs. Proteomic screens identified >600 O-GalNAc-modified proteins, but the biological relevance of these modifications has been difficult to determine. We have discovered a conserved function for GALNT3 in trophoblast stem (TS) cells, blastocyst trophectoderm, and human mammary epithelial cells (HMECs). The loss of GALNT3 expression in these systems reduces O-GalNAc glycosylation and induces epithelial-mesenchymal transition. Furthermore, Galnt3 expression is reduced in aggressive, mesenchymal claudin-low breast cancer cells. We show that GALNT3 expression controls the O-GalNAc glycosylation of multiple proteins, including E-cadherin in both TS cells and HMECs. The loss of GALNT3 results in the intracellular retention of E-cadherin in the Golgi. Significantly, re-expression of GALNT3 in TS cells increases O-GalNAc glycosylation and restores the epithelial state. Together, these data demonstrate the critical biological role of GALNT3 O-GalNAc glycosylation to promote the epithelial phenotype in TS cells, blastocyst trophectoderm, and HMECs.

show abstract

MAP3K4 Controls the Chromatin Modifier HDAC6 during Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition

Cited by 54 publications

References 25 publications

The Cxadr–Adam10 complex plays pivotal roles in tight junction integrity and early trophoblast development in mice

The Cxadr–Adam10 complex plays pivotal roles in tight junction integrity and early trophoblast development in mice

Tight Junction Assembly Ensures Maintenance of Pregnancy during Embryogenesis in a Mouse Model

GALNT3 Maintains the Epithelial State in Trophoblast Stem Cells

Contact Info

Product

Resources

About