Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microarray data of differentiating embryonic stem cells overexpressing the transcription factor Msgn1

ABSTRACT: During mammalian gastrulation, pluripotent epiblast stem cells migrate through the primitive streak to form the multipotent progenitors of the mesoderm and endoderm germ layers. Msgn1 is a bHLH transcription factor and is a direct target gene of the Wnt/bcatenin signaling pathway. Msgn1 is expressed in the mesodermal compartment of the primitive streak and is necessary for the proper development of the mesoderm. Msgn1 mutants show defects in somitogenesis leading to a lack of trunk skeletal muscles, vertebra and ribs. To study the molecular and cellular function of Msgn1 in Embryonic Stem Cells (ESC), we have generated doxycycline inducible gain-of-function ESC to overexpress Msgn1 in ESC. In order to identify Msgn1 targets, we performed transcriptional profiling of Msgn1 expressing ES cells and found that upon induction of Msgn1, multiple genes in the Notch pathway were differentially expressed compared to the uninduced cells. Moreover, Whole Mount Insitu Hybridization analysis in Msgn1 null mutants revealed that these Notch pathway genes required Msgn1 for their proper expression in vivo. Our studies demonstrate that Msgn1 is a critical effector of the Wnt pathway during mammalian somitogenesis, mediating crosstalk between the Wnt and Notch pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE29848 | GEO | 2011/07/01

SECONDARY ACCESSION(S): PRJNA140893

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Microarray data of differentiating embryonic stem cells overexpressing the transcription factor Msgn1

Project description:During mammalian gastrulation, pluripotent epiblast stem cells migrate through the primitive streak to form the multipotent progenitors of the mesoderm and endoderm germ layers. Msgn1 is a bHLH transcription factor and is a direct target gene of the Wnt/bcatenin signaling pathway. Msgn1 is expressed in the mesodermal compartment of the primitive streak and is necessary for the proper development of the mesoderm. Msgn1 mutants show defects in somitogenesis leading to a lack of trunk skeletal muscles, vertebra and ribs. To study the molecular and cellular function of Msgn1 in Embryonic Stem Cells (ESC), we have generated doxycycline inducible gain-of-function ESC to overexpress Msgn1 in ESC. In order to identify Msgn1 targets, we performed transcriptional profiling of Msgn1 expressing ES cells and found that upon induction of Msgn1, multiple genes in the Notch pathway were differentially expressed compared to the uninduced cells. Moreover, Whole Mount Insitu Hybridization analysis in Msgn1 null mutants revealed that these Notch pathway genes required Msgn1 for their proper expression in vivo. Our studies demonstrate that Msgn1 is a critical effector of the Wnt pathway during mammalian somitogenesis, mediating crosstalk between the Wnt and Notch pathways. Inducible A2lox-Flag Msgn1 ES cells were differentiated to form Embryoid bodies (EBs) for 2 days. Flag-Msgn1 was induced on day 2 with doxycycline and samples were collected at three time points, 12h, 24h and 48h after addition of doxycycline. Uninduced cells were used as controls. Experiments were performed in triplicate

2011-07-01 | E-GEOD-29848 | biostudies-arrayexpress

Genome wide occupancy of Msgn1 in differentiating embryonic stem cells

Project description:Msgn1 is a bHLH transcription factor and is a direct target gene of the Wnt/b-catenin signaling pathway. During mouse embryogenesis, Msgn1 is expressed in the mesodermal compartment of the primitive streak and is required for the differentiation of presomitic mesoderm. Msgn1-/- mutants show defects in somitogenesis leading to a lack of trunk skeletal muscles, vertebra and ribs. The goal of this study is to dissect the molecular and cellular function of Msgn1 in Embryonic Stem Cells (ESC) and mouse development. In order to identify direct Msgn1 targets, we performed transcriptional profiling and CHIP-seq of Msgn1 expressing differentiating ES cells. Integration of these data sets, we found that Msgn1 is a master regulator of PSM differentiation regulating gene expression programs of PSM identity, EMT, motility and Notch segmentation clock.

2014-09-04 | GSE55263 | GEO

Genome wide occupancy of Msgn1 in differentiating embryonic stem cells

2014-09-04 | E-GEOD-55263 | biostudies-arrayexpress

Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids

Project description:Patterning and growth are fundamental features of embryonic development that must be tightly coordinated during morphogenesis. While metabolism is known to control cell growth, how it impacts patterning and links to morphogenesis is poorly understood. To understand how metabolism impacts early mesoderm specification during gastrulation, we used in vitro mouse embryonic stem (ES) cell-derived gastruloids, due to ease of metabolic manipulations and high-throughput nature. Gastruloids showed mosaic expression of glucose transporters co-expressing with the mesodermal marker T/Bra. To understand the significance of cellular glucose uptake in development, we used the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG). 2-DG blocked the expression of T/Bra and abolishes axial elongation in gastruloids. Surprisingly, removing glucose completely from the medium did not phenocopy 2-DG treatment despite a significant decline in glycolytic intermediates occurring under both conditions. As 2-DG can also act as a competitive inhibitor of mannose in protein glycosylation, we added mannose together with 2-DG and found that it could rescue the mesoderm specification. We corroborated these results in vivomouse embryos where supplementing mannose rescued the 2-DG mediated phenotype of mesoderm specification and proximo-distal elongation of the primitive streak. We further showed that blocking production and intracellular recycling of mannose abrogated mesoderm specification. At molecular level, proteomics analysis revealed that mannose reversed glycosylation of the Wnt pathway regulator, Secreted Frizzled Receptor, Frzb, expressed in the primitive streak of the mouse embryo. Our study showed how mannose linked metabolism to glycosylation of a developmental pathway component, crucial in patterning of mesoderm and morphogenesis of gastruloids.

2024-01-12 | MSV000093849 | MassIVE

Expression profiling by high throughput sequencing (RNA sequencing)

Project description:RNAseq of CLDN6 sorted Epiblast Stem Cells (EpiSCs), WT vs Pbx1-KO lines in mouse embryonic stem cells (ES (2i/LIF and serum/LIF) and EpiSCs, as well as across differentiation (EpiSCs differentiated towards Posterior Primitive Streak (PPS) and Extraembryonic Mesoderm (ExM). Also EpiSCs treated with PD03 (MEK inhibitor) and 6h of WNT stimulation (CHIR).

2024-11-29 | E-MTAB-13618 | biostudies-arrayexpress

Patterning and gastrulation defects caused by the tw18 lethal are due to loss of Ppp2r1a

Project description:The mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors sixteen embryonic control genes identified by recessive lethal mutations isolated from wild mouse populations. Due to technical constraints so far only one of these, the tw5 lethal has been cloned and molecularly characterized. Here we report the molecular isolation of the tw18 lethal. Embryos carrying the tw18 lethal die from major gastrulation defects commencing with primitive streak formation at E6.5. We have used transcriptome and marker gene analyses to describe the molecular etiology of the tw18 phenotype. We show that both WNT and Nodal signal transduction are impaired in the mutant epiblast causing embryonic patterning defects and failure of primitive streak and mesoderm formation. We have used a candidate gene approach, gene knockout by homologous recombination and genetic rescue to identify the gene causing the tw18 phenotype as Ppp2r1a, encoding the PP2A scaffolding subunit PR65. Our work highlights the importance of phosphatase 2A in embryonic patterning, primitive streak formation, gastrulation, and mesoderm formation downstream of WNT and Nodal signaling.

2017-07-05 | GSE89734 | GEO

Expression Profile of Chicken Primitive Streak (HH4) Tissues

Project description:In birds and mammals, all mesoderm cells are generated from the primitive streak. Nascent mesoderm cells contain unique dorso-ventral (D/V) identities depending on their relative ingression position along the streak. Molecular mechanisms controlling this initial phase of mesoderm diversification are not well-understood. Using chick model, we generated high-quality transcriptomic datasets of different streak regions and analyzed their molecular heterogeneity.

2010-07-29 | GSE22230 | GEO

Dual gene activating and repressive functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation [10x scRNAseq]

Project description:Gastrulation initiates when the epiblast differentiates into either definitive ectoderm or primitive streak. During the lineage bifurcation, the DNA dioxygenase TET1 plays dual roles in both transcriptional activation and repression, but how it exerts this bipartite control via 5-methylcytosine (5mC) oxidation-dependent and independent activities remains unclear. Here, we perform a monolayer differentiation of mouse embryonic stem cells (ESCs) into neuronal precursors to define at single-cell resolution how Tet1-/- cells undergo a lineage switch to primitive streak and subsequently form mesoderm and endoderm. We identify the Wnt repressor Tcf7l1 as a direct target of TET1 that controls a signaling cascade of Wnt/β-catenin upstream of Nodal. Disrupting the endogenous catalytic site of Tet1 in ESCs contributes to activation of Nodal and subsequently Wnt/β-catenin signaling, promoting tri-lineage differentiation into ectoderm, mesoderm and endoderm. Catalytically dead TET1 is sufficient in sustaining open neuroectoderm enhancers, by which gene expression is uncoupled from enhancer DNA demethylation, and indirectly keeping primitive streak enhancers inaccessible to Wnt regulators and effectors. DNA hypermethylation caused by TET1 catalytic dysfunction instead promotes precocious primitive streak gene activation when associated with CpG islands overlapping bivalent gene promotors. Moreover, hypermethylated regions amplify in numbers in the absence of TET1 through differentiation to affect genes associated with neurological functions. Our results reveal two-way safeguarding activities of TET1 separable by genomic features, where at CpG-poor distal enhancers TET1 maintains accessible chromatin permissive for neural fate independently of 5mC oxidation; at CpG-rich bivalent promoters it prevents premature gene activation inducing alternative fates by harnessing 5mC oxidation in Polycomb gene repression.

2023-04-12 | GSE214844 | GEO