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VGLL1 regulates extraembryonic lineage specification in human [RNA-Seq]

ABSTRACT: Placenta abnormality is one of the key reasons for early pregnancy loss but the regulatory mechanisms underlying placenta formation are largely unknown. Here, we applied a human naïve pluripotent stem cell (PSC) derived TE model to explore the driven regulatory machinery. We demonstrate that VGLL1 (vestigial like family member 1) is crucial for TE self-renewal and TE-specific gene expression, thus suppressing VGLL1 leads to severely impaired cell proliferation and skewed TE induction. VGLL1 exerts its function through interacting with TEAD4 (TEA domain transcription factor 4) and colocalize at target gene promoters and enhancers. Further investigation uncovers the enrichment of H3K27ac active histone marks at genomic regions occupied by VGLL1-TEAD4 complex, indicates a close association between them. Overall, our data reveals the critical function model of VGLL1-TEAD4 in human TE derivation, highlighting a potential interspecies difference between human and mouse TE induction.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193619 | GEO | 2023/12/18

REPOSITORIES: GEO

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VGLL1 regulates extraembryonic lineage specification in human [CUT&TAG]

Project description:Placenta abnormality is one of the key reasons for early pregnancy loss but the regulatory mechanisms underlying placenta formation are largely unknown. Here, we applied a human naïve pluripotent stem cell (PSC) derived TE model to explore the driven regulatory machinery. We demonstrate that VGLL1 (vestigial like family member 1) is crucial for TE self-renewal and TE-specific gene expression, thus suppressing VGLL1 leads to severely impaired cell proliferation and skewed TE induction. VGLL1 exerts its function through interacting with TEAD4 (TEA domain transcription factor 4) and colocalize at target gene promoters and enhancers. Further investigation uncovers the enrichment of H3K27ac active histone marks at genomic regions occupied by VGLL1-TEAD4 complex, indicates a close association between them. Overall, our data reveals the critical function model of VGLL1-TEAD4 in human TE derivation, highlighting a potential interspecies difference between human and mouse TE induction.

2023-12-18 | GSE193618 | GEO

VGLL1 regulates extraembryonic lineage specification in human [ATAC-Seq]

2023-12-18 | GSE193612 | GEO

VGLL1 regulates extraembryonic lineage specification in human [RNA-seq II]

Project description:Placenta abnormality is one of the key reasons for early pregnancy loss but the regulatory mechanisms underlying placenta formation are largely unknown. Here, we applied a human naïve pluripotent stem cell (PSC) derived TE model to explore the driven regulatory machinery. We demonstrate that VGLL1 (vestigiallikefamilymember1) is crucial for TE self-renewal and TE-specific gene expression, thus suppressing VGLL1 leads to severely impaired cell proliferation and skewed TE induction. VGLL1 exerts its function through interacting with TEAD4 (TEA domain transcription factor 4) and colocalize at target gene promoters and enhancers. Further investigation uncovers the enrichment of H3K27ac active histone marks at genomic regions occupied by VGLL1-TEAD4 complex, indicates a close association between them. Overall, our data reveals the critical function model of VGLL1-TEAD4 in human TE derivation, highlighting a potential interspecies difference between human and mouse TE induction.

2023-12-18 | GSE241813 | GEO

VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification [scRNA-Seq]

Project description:In contrast to rodents, the mechanisms underlying human trophectoderm and early placenta specification are understudied due to ethical barriers and the scarcity of embryos. Recent reports have shown that human pluripotent stem cells (PSCs) can differentiate into trophectoderm (TE)-like cells (TELCs) and trophoblast stem cells (TSCs), offering a valuable in vitro model to study early placenta specification. Here, we demonstrate that the VGLL1 (vestigial-likefamilymember1), which is highly expressed during human and non-human primate TE specification in vivo but is negligibly expressed in mouse, is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs. Mechanistically, VGLL1 partners with the transcription factor TEAD4 (TEA domain transcription factor 4) to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C. Our work is relevant to understand primate early embryogenesis and how it differs from other mammalian species.

2024-01-05 | GSE252377 | GEO

VGLL1 drives therapy resistance in estrogen receptor positive breast cancer [ChIP-Seq]

Project description:The transcriptional activity of the TEAD4 trascription factor requires co-activators. In this study we found that the expression of the TEAD coactivator VGLL1 is repressed in estrogen receptor positive breast cancer but upon resistance to endocrine threapies VGLL1 is expressed to high levels. To elucidate the importance of the coactivator VGLL1 in breast cancer cells resistant to endocrine therapies and to identify the VGLL1 target genes, we performed ChIP-seq for VGLL1 in MCF7 breast cancer cells resistant to fulvestrant (FULVR) and ChiP-seq for TEAD4 in FULVR cells and the isogenic MCF7 cells.

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Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes [ChIP-seq]

Project description:Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain-containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists. The aim of this study was to evaluate the cellular function and downstream genomic targets of VGLL1 in placental, pancreatic, and breast cancer cells. Functional assays were employed to assess the role of VGLL1 in cellular invasion and proliferation, and ChIP-seq and RNA-seq assays were performed to identify VGLL1 target genes and potential impact using pathway analysis. ChIP-seq analysis identified eight transcription factors with a VGLL1-binding motif that were common between all three cell types, including TEAD1-4, AP-1, and GATA6, and revealed ~3,000 shared genes with which VGLL1 interacts. Furthermore, increased VGLL1 expression led to an enhancement of cell invasion and proliferation, which was supported by RNA-seq analysis showing transcriptional changes in several genes known to be involved in these processes. This work expands our mechanistic understanding of VGLL1 function in tumor cells and provides a strong rationale for developing VGLL1-targeted therapies for treating cancer patients.

2024-05-25 | GSE267817 | GEO

Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes [RNA-seq]

2024-05-25 | GSE267818 | GEO

VESTIGIAL-LIKE 1 IS A SHARED TARGETABLE CANCER-PLACENTA ANTIGEN EXPRESSED BY PANCREATIC AND BASAL-LIKE BREAST CANCERS

Project description:Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regression by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from tumor specimens of 35 PDAC patients. This led to the identification of a shared HLA-A*0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1), a novel putative TAA demonstrating overexpression in multiple tumor types and low or absent transcript expression in essential normal tissues. VGLL1-specific CTLs isolated and expanded from the blood of a male PDAC patient showed the capacity to recognize and kill in an antigen-specific manner a majority of HLA-A*0101 allogeneic tumor cell lines derived not only from PDAC, but also bladder, ovarian, gastric, lung and basal-like breast cancers. Gene expression profiling revealed that VGLL1 is a member of a unique group of cancer-placenta antigens (CPA) that may constitute immunotherapeutic TAA targets for patients with multiple different cancer types.

2020-10-19 | PXD018302 | Pride

Altered Subcellular Localization of Transcription Factor TEAD4 Regulates First Mammalian Cell Lineage Commitment

Project description:In the preimplantation mouse embryo TEAD4 is critical to establishing the trophectoderm (TE)-specific transcriptional program and segregating TE from the inner cell mass (ICM). However, TEAD4 is expressed both in the TE and the ICM. Thus, differential function of TEAD4 rather than expression itself regulates specification of the first two cell lineages. We used ChIP-seq to define genome-wide TEAD4 target genes and asked how transcription of TEAD4 target genes is specifically maintained in the TE. Our analyses revealed an evolutionarily conserved mechanism, in which lack of nuclear localization of TEAD4 impairs the TE-specific transcriptional program in inner blastomeres, thereby allowing their maturation towards the ICM lineage. Restoration of TEAD4 nuclear localization maintains the TE-specific transcriptional program in the inner blastomeres and prevents segregation of the TE and ICM lineages and blastocyst formation. We propose that altered subcellular localization of TEAD4 in blastomeres dictates first mammalian cell fate specification. ChIPseq profiles of TEAD4, IgG, Input in Mouse trophoblast stem cells using Illumina HiSeq 2000 and Illumina Genome Analyzer IIx

2012-04-18 | E-GEOD-37350 | biostudies-arrayexpress

VGLL1 drives therapy resistance in estrogen receptor positive breast cancer [RNA-Seq 3]

Project description:To investigate the function of VGLL1 in breast cancer and its role in the resistance to endocrine therapies we generated stable MCF7 cells overexpressing VGLL1 using CRISPR/Cas9 Synergistic Activation Mediator (SAM) method (MCF7 ActCas9-VGLL1 cells). MCF7 ActCas9-VGLL1 cells were also cultured in the presence of fulvestrant 100nmM or 1µM to develop fulvestrant resistant cells (MCF7 ActCas9-VGLL1-FULVR) and RNA-seq was performed in the different cell lines.

2023-12-05 | GSE216528 | GEO

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