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Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE227889 | GEO | 2023/12/05

REPOSITORIES: GEO

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Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation [scRNA-Seq]

Project description:In this study, we characterised transcriptomes of mESC in different conditions EPSCM and KOSR subsetting them for their single expression of SOX2 or the double expression of SOX2 and GATA6 in these conditions. 2iLIF (sorted only by DAPI negative cells) were used as control.

2023-12-05 | GSE227888 | GEO

Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation [CUT&RUN]

Project description:In early mammalian development, cleavage stage blastomeres and cells of the inner cell mass (ICM) of the blastocyst co-express embryonic and extra-embryonic transcriptional determinants. Using a double protein-based reporter we identify embryonic stem cells (ESC) that co-express the extra-embryonic factor GATA6 alongside the embryonic factor SOX2 in specific conditions. Based on single cell transcriptomics we find these population resemble unsegregated ICM, exhibiting enhanced differentiation potential for endoderm while maintaining epiblast competence and suggesting they represent an ideal model to determine how GATA6 and SOX2 influence each other's DNA binding. To relate this binding to future fate, we describe a complete enhancer set in both ESCs and naïve extraembryonic endoderm stem cells and ask whether SOX2 and GATA6 recognize these elements in ICM-like ESC sub-population. Both factors support cooperative recognition in these lineages, with GATA6 bound alongside SOX2 on a fraction of pluripotency enhancers and SOX2 alongside GATA6 more extensively on endoderm enhancers. Our findings suggest that cooperative binding between these antagonistic factors both supports self-renewal and prepares progenitor cells for later differentiation

2023-12-05 | GSE227886 | GEO

Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation

Project description:Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation

| PRJNA947234 | ENA

Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation [scRNA-Seq]

Project description:Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation [scRNA-Seq]

| PRJNA947238 | ENA

Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation [CUT&RUN]

Project description:Transcription Factor Co-Expression Mediates Lineage Priming for Embryonic and Extra-Embryonic Differentiation [CUT&RUN]

| PRJNA947237 | ENA

Dissecting embryonic and extra-embryonic lineage crosstalk with stem cell co-culture.

Project description:Faithful embryogenesis requires precise coordination between embryonic and extraembryonic tissues. Although stem cells from embryonic and extraembryonic origins have been generated for several mammalian species(Bogliotti et al., 2018; Choi et al., 2019; Cui et al., 2019; Evans and Kaufman, 1981; Kunath et al., 2005; Li et al., 2008; Martin, 1981; Okae et al., 2018; Tanaka et al., 1998; Thomson et al., 1998; Vandevoort et al., 2007; Vilarino et al., 2020; Yu et al., 2021b; Zhong et al., 2018), they are grown in different culture conditions with diverse media composition, which makes it difficult to study cross-lineage communication. Here, by using the same culture condition that activates FGF, TGF-β and WNT signaling pathways, we derived stable embryonic stem cells (ESCs), extraembryonic endoderm stem cells (XENs) and trophoblast stem cells (TSCs) from all three founding tissues of mouse and cynomolgus monkey blastocysts. This allowed us to establish embryonic and extraembryonic stem cell co-cultures to dissect lineage crosstalk during early mammalian development. Co-cultures of ESCs and XENs uncovered a conserved and previously unrecognized growth inhibition of pluripotent cells by extraembryonic endoderm cells, which is in part mediated through extracellular matrix signaling. Our study unveils a more universal state of stem cell self-renewal stabilized by activation, as opposed to inhibition, of developmental signaling pathways. The embryonic and extraembryonic stem cell co-culture strategy developed here will open new avenues for creating more faithful embryo models and developing more developmentally relevant differentiation protocols.

| S-EPMC10028955 | biostudies-literature

Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming.

Project description:Epiblast cells in the early post-implantation stage mammalian embryo undergo a transition described as lineage priming before cell fate allocation, but signaling pathways acting upstream remain ill defined. Genetic studies demonstrate that Smad2/3 double-mutant mouse embryos die shortly after implantation. To learn more about the molecular disturbances underlying this abrupt failure, here we characterized Smad2/3-deficient embryonic stem cells (ESCs). We found that Smad2/3 double-knockout ESCs induced to form epiblast-like cells (EpiLCs) display changes in naive and primed pluripotency marker gene expression, associated with the disruption of Oct4-bound distal regulatory elements. In the absence of Smad2/3, we observed enhanced Bmp target gene expression and de-repression of extra-embryonic gene expression. Cell fate allocation into all three embryonic germ layers is disrupted. Collectively, these experiments demonstrate that combinatorial Smad2/3 functional activities are required to maintain distinct embryonic and/or extra-embryonic cell identity during lineage priming in the epiblast before gastrulation.

| S-EPMC6113931 | biostudies-literature

DNA methylation restricts lineage-specific functions of transcription factor Gata4 during embryonic stem cell differentiation.

Project description:DNA methylation changes dynamically during development and is essential for embryogenesis in mammals. However, how DNA methylation affects developmental gene expression and cell differentiation remains elusive. During embryogenesis, many key transcription factors are used repeatedly, triggering different outcomes depending on the cell type and developmental stage. Here, we report that DNA methylation modulates transcription-factor output in the context of cell differentiation. Using a drug-inducible Gata4 system and a mouse embryonic stem (ES) cell model of mesoderm differentiation, we examined the cellular response to Gata4 in ES and mesoderm cells. The activation of Gata4 in ES cells is known to drive their differentiation to endoderm. We show that the differentiation of wild-type ES cells into mesoderm blocks their Gata4-induced endoderm differentiation, while mesoderm cells derived from ES cells that are deficient in the DNA methyltransferases Dnmt3a and Dnmt3b can retain their response to Gata4, allowing lineage conversion from mesoderm cells to endoderm. Transcriptome analysis of the cells' response to Gata4 over time revealed groups of endoderm and mesoderm developmental genes whose expression was induced by Gata4 only when DNA methylation was lost, suggesting that DNA methylation restricts the ability of these genes to respond to Gata4, rather than controlling their transcription per se. Gata4-binding-site profiles and DNA methylation analyses suggested that DNA methylation modulates the Gata4 response through diverse mechanisms. Our data indicate that epigenetic regulation by DNA methylation functions as a heritable safeguard to prevent transcription factors from activating inappropriate downstream genes, thereby contributing to the restriction of the differentiation potential of somatic cells.

| S-EPMC3694845 | biostudies-literature

Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming

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

2018-08-14 | GSE110164 | GEO

The forkhead transcription factor FOXK2 premarks lineage-specific genes in human embryonic stem cells for activation during differentiation.

Project description:Enhancers play important roles in controlling gene expression in a choreographed spatial and temporal manner during development. However, it is unclear how these regulatory regions are established during differentiation. Here we investigated the genome-wide binding profile of the forkhead transcription factor FOXK2 in human embryonic stem cells (ESCs) and downstream cell types. This transcription factor is bound to thousands of regulatory regions in human ESCs, and binding at many sites is maintained as cells differentiate to mesendodermal and neural precursor cell (NPC) types, alongside the emergence of new binding regions. FOXK2 binding is generally associated with active histone marks in any given cell type. Furthermore newly acquired, or retained FOXK2 binding regions show elevated levels of activating histone marks following differentiation to NPCs. In keeping with this association with activating marks, we demonstrate a role for FOXK transcription factors in gene activation during NPC differentiation. FOXK2 occupancy in ESCs is therefore an early mark for delineating the regulatory regions, which become activated in later lineages.

| S-EPMC7897486 | biostudies-literature

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