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Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells

ABSTRACT: Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells

PROVIDER: PRJNA861235 | ENA |

REPOSITORIES: ENA

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Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (ChIP-seq)

Project description:The placenta is an organ with extraordinary phenotypic diversity in eutherian mammals. Recent evidence suggest that numerous human placental enhancers are evolved from lineage-specific insertions of endogenous retroviruses (ERVs), yet the transcription factors (TFs) underlying their regulation remain largely elusive. Here, by first focusing on MER41, a primate-specific ERV family previously linked to placenta and innate immunity, we uncover the binding motifs of multiple crucial trophoblast TFs (GATA2/3, MSX2, GRHL2) in addition to innate immuninty TFs STAT1 and IRF1. Integration of ChIP-Seq data confirms the binding of GATA2/3 and MSX2 on the majority of MER41-derived enhancers in human trophoblast stem cells (TSCs). Notably, the usb-family composition of MER41-derived enhancers that are active in human TSCs are distinct from those activated upon interferon stimulation, which is determined by the binding of trophoblast TFs. We further demonstrate that GATA2/3 and MSX2 have prevalent binding on numerous other ERV families – indicating their broad impact on ERV-derived placental enhancers. Functionally, the derepression of many syncytiotrophoblast genes after disruption of MSX2 is likely to be mediated by enhancers derived from ERVs – suggesting ERVs are also important for mediating transcriptional repression in human TSCs. Overall, this study characterized the prevalent binding of GATA2/3, MSX2 and their co-factors on ERV-derived enhancers in human TSCs and provided mechanistic insights into the importance of ERVs in human trophoblast regulatory network.

2023-01-01 | GSE209540 | GEO

Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (RNA-seq)

2023-01-01 | GSE209536 | GEO

Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (ChIP-seq)

Project description:Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (ChIP-seq)

| PRJNA861387 | ENA

Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (RNA-seq)

Project description:Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (RNA-seq)

| PRJNA861391 | ENA

Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-01 | GSE209541 | GEO

MSX2 safeguards syncytiotrophoblast fate of human TSCs

Project description:The majority of placental pathologies arise from failures in trophoblast differentiation, yet the underlying transcriptional regulation is poorly understood. Here, we use human trophoblast stem cells to elucidate the function of the transcription factor MSX2 in trophoblast specification. We show that depletion of MSX2 de-represses the syncytiotrophoblast program, while forced expression of MSX2 blocks it. We demonstrate that a large proportion of the affected genes are directly bound and regulated by MSX2 and identify components of the SWI/SNF complex as its strong interactors. Our findings uncover the pivotal role of MSX2 in cell fate decisions that govern human placental development and function.

2021-08-28 | GSE165970 | GEO

Specificity protein 6 governs human cytotrophoblast fate decisions and trophoblast stem cell establishment by targeting MSX2 regulatory elements [RNA-seq]

Project description:The commitment and differentiation of human placental progenitor cytotrophoblast (CT) cells are crucial for a successful pregnancy, but the underlying regulatory mechanism remains poorly understood. Here we identified the transcription factor (TF), Specificity protein 6 (SP6), as a human species-specific trophoblast lineage TF expressed in human placental CT cells. Using pluripotent stem cells as a model, we demonstrated that SP6 governs CT generation and the establishment of trophoblast stem cells (TSCs) and discovered msh homeobox 2 (MSX2) as the downstream effector in these events. Mechanistically, we showed that SP6 interacts with histone acetyltransferase P300 to modulate the landscape of H3K27ac at targeted regulatory elements, thereby favoring transcriptional activation and facilitating CT cell fate decisions and TSC maintenance. Our results established SP6 as a novel regulator of the human trophoblast lineage and implied its regulatory role in placental development and the pathogenies of placental diseases.

2024-03-11 | GSE236795 | GEO

Specificity protein 6 governs human cytotrophoblast fate decisions and trophoblast stem cell establishment by targeting MSX2 regulatory elements [ChIP-seq]

2024-03-11 | GSE236794 | GEO

RNA-Seq analysis in human trophoblast stem cells (CT27) upon depletion of transcription factor GATA2 or GATA3

Project description:The GATA transcription factors, particularly GATA2 and GATA3 are responsible for trophoblast stem cells self renewal and differentiation in mice. However, we have a poor understanding about the contribution of GATA2 and GATA3, in the trophoblast cells in humans. Thus, the goal of this study is to define the importance of GATA factors in orchestrating global gene expression program in human trophoblast stem cells. Using a RNA interference strategy (RNAi), we depleted GATA2 or GATA3 expression in human trophoblast stem cells (GATA2 KD or GATA3 KD) . We then differentiated GATA2 KD and GATA3 KD human trophoblast stem cells into syncytiotrophoblasts(SynT) and compared global gene expression patterns via RNA sequencing (RNA-seq). Three individual experiments were performed for the differentiated SynT state. The submitted files contain the data (raw fastq files, count data and deseq2 output) from those experiments.

2024-01-26 | GSE214634 | GEO

Cut and run analysis in human trophoblast stem cells (CT27) upon pulling down with GATA2 and GATA3 antibody

Project description:GATA transcription factors, particularly GATA2 and GATA3 are selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast self-renewal during mammalian development. However, we have a poor understanding about the contribution of these GATA factors, in the process of syncytiotrophoblast (SynT) development. Thus, the goal of this study is to define the importance of GATA2 and GATA3 in orchestrating a global gene expression program that poises and commits mammalian trophoblast stem cells to the SynT lineage. Using the cut and run technique for GATA2 and GATA3 antibodies in the human trophoblast stem cells we are aiming to identify the direct targets of the GATA transcription factors that are essential for determining the SynT lineage. Three individual experiments were performed.

2024-01-26 | GSE214486 | GEO

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