Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lysophosphatidic Acid Accelerates Bovine In Vitro-Produced Blastocyst Formation through the Hippo/YAP Pathway.

ABSTRACT: The segregation of trophectoderm (TE) and inner cell mass in early embryos is driven primarily by the transcription factor CDX2. The signals that trigger CDX2 activation are, however, less clear. In mouse embryos, the Hippo-YAP signaling pathway is important for the activation of CDX2 expression; it is less clear whether this relationship is conserved in other mammals. Lysophosphatidic acid (LPA) has been reported to increase YAP levels by inhibiting its degradation. In this study, we cultured bovine embryos in the presence of LPA and examined changes in gene and protein expression. LPA was found to accelerate the onset of blastocyst formation on days 5 and 6, without changing the TE/inner cell mass ratio. We further observed that the expression of TAZ and TEAD4 was up-regulated, and YAP was overexpressed, in LPA-treated day 6 embryos. However, LPA-induced up-regulation of CDX2 expression was only evident in day 8 embryos. Overall, our data suggest that the Hippo signaling pathway is involved in the initiation of bovine blastocyst formation, but does not affect the cell lineage constitution of blastocysts.

SUBMITTER: Yu B

PROVIDER: S-EPMC8198578 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Lysophosphatidic acid signaling in late cleavage and blastocyst stage bovine embryos.

Project description:Lysophosphatidic acid (LPA) is a known cell signaling lipid mediator in reproductive tissues. In the cow, LPA is involved in luteal and early pregnancy maintenance. Here, we evaluated the presence and role of LPA in bovine early embryonic development. In relevant aspects, bovine embryos reflect more closely the scenario occurring in human embryos than the mouse model. Transcription of mRNA and protein expression of enzymes involved in LPA synthesis (ATX and cPLA2) and of LPA receptors (LPAR1-4) were detected in Days 5 and 8 in vitro produced embryos. Embryonic LPA production into culture medium was also detected at both stages of development. Supplementation of culture medium with LPA (10(-5) M) between Days 2 and 8 had no effect on embryo yield and quality and on blastocyst relative mRNA abundance of genes involved in prostaglandin synthesis (PTGS2, PGES, and PGFS) and steroidogenesis (3βHSD). However, LPA treatment affected transcription levels of embryo quality markers, decreasing BAX (apoptotic) and increasing BCL2 (antiapoptotic) and IGF2R (growth marker) gene transcription levels. Blastocyst transcription of OCT4 (pluripotency marker) was not affected by LPA stimulation. In conclusion, LPA is an early bovine embryonic autocrine/paracrine signaling mediator, and LPA action may be relevant in early embryo-maternal interactions leading to embryonic survival.

| S-EPMC4009307 | biostudies-literature

The Hippo pathway effectors YAP and TAZ interact with EGF-like signaling to regulate expansion-related events in bovine cumulus cells in vitro.

Project description:PurposeTo determine if the inhibition of the interaction between the Hippo effector YAP or its transcriptional co-activator TAZ with the TEAD family of transcription factors is critical for the cumulus expansion-related events induced by the EGF network in cumulus-oocyte complexes (COCs).MethodsWe performed a series of experiments using immature bovine COCs subjected to an IVM protocol for up 24 h in which cumulus expansion was stimulated with EGF recombinant protein or FSH.ResultsThe main results indicated that EGFR activity stimulation in bovine cumulus cells (CC) increases mRNA levels encoding the classic YAP/TAZ-TEAD target gene CTGF. To determine if important genes for cumulus expansion are transcriptional targets of YAP/TAZ-TEAD interaction in CC, COCs were then subjected to IVM in the presence of FSH with or without distinct concentrations of Verteporfin (VP; a small molecule inhibitor that interferes with YAP/TAZ binding to TEADs). COCs were then collected at 6, 12, 18, and 24 h for total RNA extraction and RT-qPCR analyses. This experiment indicated that VP inhibits in a time- and concentration-dependent manner distinct cumulus expansion and oocyte maturation-related genes, by regulating EGFR and CTGF expression in CC.ConclusionsTaken together, the results presented herein represent considerable insight into the functional relevance of a completely novel signaling pathway underlying cumulus expansion and oocyte maturation in monovulatory species. YAP/TAZ or CTGF may represent potential targets to improve the efficiency of IVM systems, not only for monovulatory species of agricultural importance as the cow, but for human embryo production.

| S-EPMC8956774 | biostudies-literature

YAP and the Hippo pathway in cholangiocarcinoma.

Project description:Cholangiocarcinoma (CCA) has an increasing incidence and remains a difficult to treat malignancy. In a search for more effective treatment options, progress has been made in identifying molecular drivers of oncogenic signaling including IDH mutations and FGFR2 fusions. In addition, multiple investigators have identified increased activity of YAP, the effector protein of the Hippo pathway, in CCA. The Hippo pathway regulates organ size, cellular proliferation, and apoptosis via YAP, a transcriptional co-activator. Targeting of the pathway has been difficult due the lack of a dedicated cell-surface receptor. However, more recently, additional cross-regulatory pathways have been identified that are potentially targetable. In this review, we address the current treatment landscape for CCA, the Hippo pathway broadly, animal models of CCA with attention to Hippo-related models, and the current strategies for targeting YAP.

| S-EPMC6536462 | biostudies-literature

Hippo pathway effector Yap promotes cardiac regeneration.

Project description:The adult mammalian heart has limited potential for regeneration. Thus, after injury, cardiomyocytes are permanently lost, and contractility is diminished. In contrast, the neonatal heart can regenerate owing to sustained cardiomyocyte proliferation. Identification of critical regulators of cardiomyocyte proliferation and quiescence represents an important step toward potential regenerative therapies. Yes-associated protein (Yap), a transcriptional cofactor in the Hippo signaling pathway, promotes proliferation of embryonic cardiomyocytes by activating the insulin-like growth factor and Wnt signaling pathways. Here we report that mice bearing mutant alleles of Yap and its paralog WW domain containing transcription regulator 1 (Taz) exhibit gene dosage-dependent cardiac phenotypes, suggesting redundant roles of these Hippo pathway effectors in establishing proper myocyte number and maintaining cardiac function. Cardiac-specific deletion of Yap impedes neonatal heart regeneration, resulting in a default fibrotic response. Conversely, forced expression of a constitutively active form of Yap in the adult heart stimulates cardiac regeneration and improves contractility after myocardial infarction. The regenerative activity of Yap is correlated with its activation of embryonic and proliferative gene programs in cardiomyocytes. These findings identify Yap as an important regulator of cardiac regeneration and provide an experimental entry point to enhance this process.

| S-EPMC3752208 | biostudies-literature

Gene expression profile of in vitro produced bovine blastocyst with and without Thyroid hormone supplementation

Project description:Bovine IVP blastocysts (day 8) were produced with and without thyroid hormones and gene expression profiles were compared.

2014-09-01 | GSE58901 | GEO

Embryonic POU5F1 is Required for Expanded Bovine Blastocyst Formation.

Project description:POU5F1 is a transcription factor and master regulator of cell pluripotency with indispensable roles in early embryo development and cell lineage specification. The role of embryonic POU5F1 in blastocyst formation and cell lineage specification differs between mammalian species but remains completely unknown in cattle. The CRISPR/Cas9 system was utilized for targeted disruption of the POU5F1 gene by direct injection into zygotes. Disruption of the bovine POU5F1 locus prevented blastocyst formation and was associated with embryonic arrest at the morula stage. POU5F1 knockout morulas developed at a similar rate as control embryos and presented a similar number of blastomeres by day 5 of development. Initiation of SOX2 expression by day 5 of development was not affected by lack of POU5F1. On the other hand, CDX2 expression was aberrant in embryos lacking POU5F1. Notably, the phenotype observed in bovine POU5F1 knockout embryos reveals conserved functions associated with loss of human embryonic POU5F1 that differ from Pou5f1- null mice. The similarity observed in transcriptional regulation of early embryo development between cattle and humans combined with highly efficient gene editing techniques make the bovine a valuable model for human embryo biology with expanded applications in agriculture and assisted reproductive technologies.

| S-EPMC5958112 | biostudies-literature

Gene expression profile of in vitro produced bovine blastocyst with and without Thyroid hormone supplementation

Project description:Bovine IVP blastocysts (day 8) were produced with and without thyroid hormones and gene expression profiles were compared. The IVC media (SOF) was supplemented with 50ng/ml of each T3 and T4. Four independent IVF run, each gave 1 control and 1 treated sample. Each sample is a pool of 5 blastocyst. Total Rna was extracted from each sample, amplified, labeled (also with dye swap) and hybridized to the EmbryoGene custom Agilent array (GPL13226). FlexArray software was used for data analysis.

2014-09-01 | E-GEOD-58901 | biostudies-arrayexpress

The Crosstalk Between Hippo-YAP Pathway and Innate Immunity.

Project description:Recognition of pathogen-associated molecular patterns (PAMPs) triggers expression of antiviral interferons and proinflammatory cytokines, which functions as the frontier of host defense against microbial pathogen invasion. Hippo-YAP pathway regulates cell proliferation, survival, differentiation and is involved in diverse life processes, including tissue homeostasis and tumor suppression. Emerging discoveries elucidated that the components of Hippo-YAP pathway, such as MST1/2, NDR1/2, and YAP/TAZ played crucial regulatory roles in innate immunity. Meanwhile the innate immune signaling also exhibited regulatory effect on Hippo-YAP pathway. As for the importance of these two pathways, it would be interesting to figure out the deeper biological implications of their interplays. This review focuses on the regulation between Hippo-YAP pathway and innate immune signaling. We also propose the possible contribution of these interplays to tumor development.

| S-EPMC7056731 | biostudies-literature

Hippo pathway effector Yap is an ovarian cancer oncogene.

Project description:The Hippo pathway regulates organ size and tumorigenesis in Drosophila and mammals and is altered in a variety of human cancers, yet it remains unclear if the Hippo pathway is of prognostic significance to cancer patients. Here we show that the key targets of Hippo signaling, transcriptional coactivators Yki and Yap, play a conserved role in promoting ovarian cancer in flies and humans, respectively. Whereas studies linking Yap to cancer in other tissues have focused on overall Yap levels, we show for the first time that subcellular levels of Yap show an exceptionally strong association with poor patient survival. Specifically, high levels of nuclear Yap (nYap), or low levels of cytoplasmic phosphorylated Yap (cpYap), associated with poor survival from ovarian cancer. Patients with both high nYap and low cpYap had ?50% lower 5-year survival, and this combination is an independent prognostic marker for survival, with an exceptionally high hazard ratio of 7.8. We find that Yap2 is the predominantly expressed Yap isoform in both the ovarian surface epithelium (OSE) and epithelial ovarian cancers. Overexpression of Yap2 and phosphorylation-defective Yap2-5SA in immortalized OSE cells resulted in increased cell proliferation, resistance to cisplatin-induced apoptosis, faster cell migration, and anchorage-independent growth, whereas Yap knockdown resulted in increased sensitivity to cisplatin-induced apoptosis. Findings argue that the Hippo signaling pathway defines an important pathway in progression of ovarian cancer.

| S-EPMC2970655 | biostudies-literature

Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation.

Project description:Invadopodia are adhesive, actin-rich protrusions formed by metastatic cancer cells that degrade the extracellular matrix and facilitate invasion. They support the metastatic cascade by a spatially and temporally coordinated process whereby invading cells bind to the matrix, degrade it by specific metalloproteinases, and mechanically penetrate diverse tissue barriers by forming actin-rich extensions. However, despite the apparent involvement of invadopodia in the metastatic process, the molecular mechanisms that regulate invadopodia formation and function are still largely unclear. In this study, we have explored the involvement of the key Hippo pathway co-regulators, namely YAP, and TAZ, in invadopodia formation and matrix degradation. Toward that goal, we tested the effect of depletion of YAP, TAZ, or both on invadopodia formation and activity in multiple human cancer cell lines. We report that the knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Collectively, our findings show that YAP and TAZ act as negative regulators of invadopodia formation in diverse cancer lines, most likely by reducing the levels of essential invadopodia components. Dissecting the molecular mechanisms of invadopodia formation in cancer invasion may eventually reveal novel targets for therapeutic applications against invasive cancer.

| S-EPMC10130049 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data