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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Lsd1 coordinates trophoblast development by retaining stem cells in their niche and directing cell fate

ABSTRACT: Stem cells reside in specific niches providing stemness-maintaining environments. Thus, the regulated migration from these niches is associated with differentiation onset. However, mechanisms retaining stem cells in their niche remain poorly understood. Here, we show that the epigenetic regulator lysine-specific demethylase 1 (Lsd1) organises the trophoblast niche of the early mouse embryo by coordinating migration and invasion of trophoblast stem cells (TSCs). Lsd1 deficiency leads to the depletion of the stem cell pool resulting from precocious migration of TSCs. Migration is induced by premature expression of the transcription factor Ovol2 that is repressed by Lsd1 in undifferentiated wild-type TSCs. Increasing Ovol2 levels suffices to recapitulate the migration phenotype. Furthermore, Lsd1-deficient TSCs exhibit a developmental bias towards cells of the syncytiotrophoblast and impaired spongiotrophoblast and trophoblast giant cell differentiation. In summary, we describe that the epigenetic modifier Lsd1 coordinates placental development by retaining TSCs in their niche and directing trophoblast differentiation. Mouse trophoblast stem cells (TSCs) were isoloated from a single conditional Lsd1-deficient mouse (Lsd1tm1SchM-CM-

ORGANISM(S): Mus musculus

SUBMITTER: Thomas GM-CM-<nther

PROVIDER: E-GEOD-38277 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Lsd1 coordinates trophoblast development by retaining stem cells in their niche and directing cell fate

Project description:Stem cells reside in specific niches providing stemness-maintaining environments. Thus, the regulated migration from these niches is associated with differentiation onset. However, mechanisms retaining stem cells in their niche remain poorly understood. Here, we show that the epigenetic regulator lysine-specific demethylase 1 (Lsd1) organises the trophoblast niche of the early mouse embryo by coordinating migration and invasion of trophoblast stem cells (TSCs). Lsd1 deficiency leads to the depletion of the stem cell pool resulting from precocious migration of TSCs. Migration is induced by premature expression of the transcription factor Ovol2 that is repressed by Lsd1 in undifferentiated wild-type TSCs. Increasing Ovol2 levels suffices to recapitulate the migration phenotype. Furthermore, Lsd1-deficient TSCs exhibit a developmental bias towards cells of the syncytiotrophoblast and impaired spongiotrophoblast and trophoblast giant cell differentiation. In summary, we describe that the epigenetic modifier Lsd1 coordinates placental development by retaining TSCs in their niche and directing trophoblast differentiation.

2014-01-17 | GSE38277 | GEO

scRNA-seq and snucRNA-seq of human primary trophoblast organoids (PTO) and trophoblast stem cells (TSCs) differentiation into extravillous trophoblast organoids (EVTs)

Project description:This study aims to compare in vivo human trophoblast differentiation into EVTs to different in vitro trophoblast organoids using single-cell and single-nuclei RNA sequencing. The study includes two type of systems: human primary trophoblast organoids (PTO) and trophoblast stem cells (TSCs). Trophoblast stem cell (TSC) lines BTS5 and BTS11 derived by Okae and colleagues were grown as described previously (Okae et al. 2018) and together with EVT media. Primary trophoblast organoids (PTO) were grown and differentiated into EVT as previously described by Turco & Sheridan (Turco et al 2018; Sheridan et al 2020). This study shows that the main regulatory programs mediating EVT invasion in vivo are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells.

2023-02-09 | E-MTAB-12650 | biostudies-arrayexpress

The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate

Project description:Here, we demonstrate that upon inhibition of the Fgf/Erk pathway in mouse trophoblast stem cells (TSCs), the Ets2 repressor factor (Erf) interacts with components of the Nuclear Receptor Corepressor Complex 1 and 2 (NCoR1 and NCoR2). Upon attenuation of Fgf signalling, unphosphorylated, nuclear Erf recruits the NCoR1/2 complex to key trophoblast genes, brings about their transcriptional silencing and facilitates differentiation and placental development.

2023-04-26 | PXD037892 | Pride

Gene expression profiling reveals a novel regulatory role for Sox21 in mouse trophoblast stem cell differentiation.

Project description:In this study we introduced Sox21 as a new regulator of trophoblast stem cell (TSC) differentiation. The transcriptome of different cell types were analyzed and compared to identify a TSC gene signature. In order to identify novel TSC specific genes, we performed genome-wide expression profiling of TSCs, embryonic stem cells, epiblast stem cells, and mouse embryo fibroblasts derived from mice of the same genetic background (129S1/SvImJ).

2015-11-10 | E-GEOD-67037 | biostudies-arrayexpress

CTCF binding patterns in mouse trophoblast stem cells

Project description:This Series reports data from a CTCF ChIP-Seq experiment performed in F1-hybrid mouse trophoblast stem cells (TSCs). The data are part of a larger study examining inactive X gene expression and chromatin states, reported as GEO Series GSE39406. Included for this dataset are FASTQ files, BED alignments and WIG files with coordinates relative to UCSC genome build mm9, and _snp files that report the location of all SNP-overlapping reads Single CTCF ChIP-Seq experiment

2012-09-08 | E-GEOD-40667 | biostudies-arrayexpress

Defining principles of gene and regulatory element imprinting in mouse trophoblast stem cells

Project description:An undefined number of mammalian genes are expressed preferentially from one parental allele, in a process termed genomic imprinting. To shed light on the general principles of this process in a single cell type, we profiled allelic gene expression, DNaseI hypersensitivity (DHS), and CTCF binding in genetically defined murine trophoblast stem cells (TSCs). The data deposited in this entry are from CTCF ChIP-Seq and DNase-Seq experiments performed in the BC.1 cell line. All other data has been previously deposited as part of GEO Series GSE39406. The F1 TSC line profiled was generated from a cross between a C57BL/6J (B6) female and CAST/EiJ (Cast) male mouse.

2016-07-03 | E-GEOD-51610 | biostudies-arrayexpress

EGAS00001004722-2-sc-2023-02-01T09:39:21Z - samples

Project description:This dataset is part of a study that aims to compare in vivo human trophoblast differentiation into EVTs to different in vitro trophoblast organoids using single-cell and single-nuclei RNA sequencing. This specific dataset includes scRNA-seq and snRNA-seq data from trophoblast stem cells (TSCs). Trophoblast stem cell (TSC) lines BTS5 and BTS11 derived by Okae and colleagues were grown as described previously (Okae et al. 2018) together with EVT differentiation media. This study shows that the main regulatory programs mediating EVT invasion in vivo are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells. Data for primary trophoblast organoids is available under E-MTAB-12650.

| EGAD00001010017 | EGA

Site-specific silencing of regulatory elements as a mechanism of X-inactivation

Project description:The inactive X chromosome’s (Xi) physical territory is microscopically devoid of transcriptional hallmarks and enriched in silencing-associated modifications. How these microscopic signatures relate to specific Xi sequence is unknown. This study reports the profiling of Xi gene expression and chromatin states at high-resolution via allele-specific sequencing in F1 hybrid mouse trophoblast stem cells (TSCs). Datasets provided include those generated from strand-specific RNA-Seq, ChIP-Seq, FAIRE-Seq, and DNase-Seq protocols. Included for each dataset are FASTQ files, BED alignments and WIG files with coordinates relative to UCSC genome build mm9, and _snp files that report the location of all SNP-overlapping reads. The F1 TSC lines profiled were generated from crosses between CAST/EiJ (Cast) and C57BL/6J (B6) mice. C/B denotes a Cast mother and B6 father, and B/C denotes a B6 mother and Cast father.

2012-11-21 | E-GEOD-39406 | biostudies-arrayexpress

Gata3 acts alongside Cdx2 to promote trophoblast gene expression downstream of Tead4 during mouse development

Project description:The first lineage decisions during mouse development lead to establishment of embryonic and extraembryonic tissues. The transcription factor Cdx2 plays a central role by repressing pluripotency genes, such as Oct4 and promoting trophoblast fate at the blastocyst stage. Here we show that the transcription factor Gata3 is coexpressed with Cdx2 in the blastocyst and that overexpression of Gata3 in embryonic stem cells is sufficient to induce expression of trophoblast genes. Gata3 expression in the blastocyst does not depend on Cdx2, nor do Gata3 overexpressing cell lines require Cdx2 for expression of a subset of trophoblast genes. In the embryo, expression of Gata3, like Cdx2, depends on Tead4, and expression of both factors becomes restricted to nascent trophoblast by an Oct4-independent mechanism. These observations place Tead4 at the top of a trophoblast hierarchy, with Gata3 and Cdx2 acting downstream to induce expression of common and independent targets in this lineage. This SuperSeries is composed of the following subset Series: GSE12985: Differentiation time course of trophoblast stem cells GSE12986: Expression of Cdx2 or Gata3 in R1 mouse embryonic stem cells

2010-02-21 | E-GEOD-12999 | biostudies-arrayexpress

Mouse trophoblast stem cells in KSR-based conditions

Project description:We have constituted the serum-free culture conditions (SFC) with Knockout Serum Replacement that support growth of mouse trophoblast stem cells (TSCs). The global gene expression profile of undifferentiated TSCs was maintained in the SFC. TSCs in the SFC showed differentiation potential both in vitro and in vivo.

2020-09-30 | GSE147023 | GEO

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