Mouse trophoblast stem cells in KSR-based conditions
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE147023 | GEO | 2020/09/30
REPOSITORIES: GEO
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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. Mouse trophoblast stem cells (TSCs) were isoloated from a single conditional Lsd1-deficient mouse (Lsd1tm1SchM-CM-<le). Deletion of Lsd1 was induced eight days before the collection of RNA by addition of 0.2 M-BM-5M 4OH-tamoxife. Cells were isolated at successive stages of differentiation for total RNA extraction and hybridization on Affymetrix microarrays. To that end, we harvested cells at three time-points: before induction of differentiation (d0), two days after induction of differentiation (d2), and four days after induction of differentiation (d4). Three replicates (1, 2, 3) for control (-) and Lsd1-deficeint (+) cells were included for each differentiation stage.
2014-01-17 | E-GEOD-38277 | biostudies-arrayexpress
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
Project description:The inner cell mass (ICM) and trophoblast cell lineages duet early embryonic development in mammals. After implantation, the ICM forms the embryo proper as well as some extraembryonic tissues, whereas the trophoectoderm (TE) exclusively forms the fetal portion of the placenta and the trophoblast giant cells. Although embryonic stem (ES) cells can be derived from ICM in cultures of mouse blastocysts in the presence of LIF and/or combinations of small-molecule chemical compounds, and the undifferentiated pluripotent state can be stably maintained without use of serum and feeder cells, defined culture conditions for derivation and maintenance of undifferentiated trophoblast stem (TS) cells have not been established. Here, we report that addition of FGF2, activin A, XAV939, and Y27632 are necessary and sufficient for derivation of TS cells from both of E3.5 blastocysts and E6.5 early postimplantation extraembryonic ectoderm. Moreover, the undifferentiated TS cell state can be stably maintained in chemically defined culture conditions. Cells derived in this manner expressed TS cell marker genes, including Eomes, Elf5, Cdx2, Klf5, Cdh1, Esrrb, Sox2, and Tcfap2c; differentiated into all trophoblast subtypes (trophoblast giant cells, spongiotrophoblast, and labyrinthine trophoblast) in vitro; and exclusively contributed to trophoblast lineages in chimeric animals. This delineation of minimal requirements for derivation and self-renewal provides a defined platform for precise description and dissection of the molecular state of TS cells.
2014-07-08 | GSE59107 | GEO
Project description:The inner cell mass (ICM) and trophoblast cell lineages duet early embryonic development in mammals. After implantation, the ICM forms the embryo proper as well as some extraembryonic tissues, whereas the trophoectoderm (TE) exclusively forms the fetal portion of the placenta and the trophoblast giant cells. Although embryonic stem (ES) cells can be derived from ICM in cultures of mouse blastocysts in the presence of LIF and/or combinations of small-molecule chemical compounds, and the undifferentiated pluripotent state can be stably maintained without use of serum and feeder cells, defined culture conditions for derivation and maintenance of undifferentiated trophoblast stem (TS) cells have not been established. Here, we report that addition of FGF2, activin A, XAV939, and Y27632 are necessary and sufficient for derivation of TS cells from both of E3.5 blastocysts and E6.5 early postimplantation extraembryonic ectoderm. Moreover, the undifferentiated TS cell state can be stably maintained in chemically defined culture conditions. Cells derived in this manner expressed TS cell marker genes, including Eomes, Elf5, Cdx2, Klf5, Cdh1, Esrrb, Sox2, and Tcfap2c; differentiated into all trophoblast subtypes (trophoblast giant cells, spongiotrophoblast, and labyrinthine trophoblast) in vitro; and exclusively contributed to trophoblast lineages in chimeric animals. This delineation of minimal requirements for derivation and self-renewal provides a defined platform for precise description and dissection of the molecular state of TS cells. Total RNA was purified by using RNeasy Mini kit (QIAGEN). Microarray targets from 200 ng total RNA were synthesized and labelled using the Low RNA Input Linear Amp Kit (Agilent) and hybridized to Mouse 4x44K Ver.2.0 arrays. Arrays were scanned on an Agilent Technologies Microarray scanner and signal intensities were calculated in Agilent Feature Extraction 10.7.3.1 software.
2014-07-08 | E-GEOD-59107 | biostudies-arrayexpress
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
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
Project description:In this experiment, the effect of reduced CDX2 expression on the trophoblast stem cells (TSCs) transcriptome was assayed.
2022-07-01 | GSE181056 | GEO
Project description:In this experiment, the effect of reduced CDX2 expression on chromatin accessibility in trophoblast stem cells (TSCs) was assayed using ATAC-seq.
2022-07-01 | GSE181053 | GEO
Project description:The arising of trophectoderm (TE) is a hallmark event in preimplantation development during embryogenesis. However, little is known about the mechanisms underlying TE specification. Our findings demonstrate that depletion of Rif1 breaks down the barriers to conversion of trophoblast stem cells (TSCs). Rif1-null induced TSCs show typical TE properties, and differentiation potentials to terminal trophoblast lineages. Global transcriptome analysis reveals that Rif1-null activates 2-cell embryo (2C) related genes and induces a totipotent-like state, which is probably the main reason for the conversion of TSCs from Rif1-null embryonic stem cells (ESCs). Chimeric assays further confirm that Rif1-null ESCs can contribute to TE, further yielding TSCs in vitro. Over-expression of a downstream gene of Rif1, Hmgn3, can also activate 2C related genes and facilitate induction of TSCs. Here, we report two pioneer genes regulating conversion of TSCs and provide insights for investigating the mechanisms of TE specification.
2021-12-01 | GSE189683 | GEO
Project description:We found that PI3K inhibition increased the expression of stem cell markers in trophoblast stem cells (TSCs). To better understand the PI3K inhibited cells, we compared untreated TSCs with cells treated with PI3K inhibitor ZSTK474 for 3h, 6h and 3 days.
2019-05-30 | GSE125301 | GEO