Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Coordination of germ-layer lineage choice by TET1 during primed pluripotency (ChIP-seq)

ABSTRACT: Gastrulation in the early post-implantation stage mammalian embryo begins when epiblast cells ingress to form the primitive streak or develop as the embryonic ectoderm. The DNA dioxygenase Tet1 is highly expressed in the epiblast and yet continues to regulate lineage specification during gastrulation when its expression is diminished. Here, we show how Tet1 plays a pivotal role upstream of germ layer lineage bifurcation. During the transition from naive pluripotency to lineage priming, a global reconfiguration re-distributes Tet1 from Oct4 co-bound promoters to distal regulatory elements at lineage differentiation genes which are distinct from high-affinity sites engaged by Oct4. An altered chromatin landscape in Tet1-deficient primed epiblast-like cells is associated with enhanced Oct4 expression and binding to Nodal and Wnt target genes, resulting in collaborative signals that enhance mesendodermal and inhibit neuroectodermal gene expression during lineage segregation. A permissive role for Tet1 in neural fate induction involves Zic2-dependent engagement at neural target genes at lineage priming, is dependent on the signaling environment during gastrulation and impacts neural tube closure at post-gastrulation. Our findings provide mechanistic information for epigenetic integration of pluripotency and signal-induced differentiation cues.

ORGANISM(S): Mus musculus

PROVIDER: GSE144868 | GEO | 2020/03/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Coordination of germ-layer lineage choice by TET1 during primed pluripotency (ATAC-seq)

Project description:Gastrulation in the early post-implantation stage mammalian embryo begins when epiblast cells ingress to form the primitive streak or develop as the embryonic ectoderm. The DNA dioxygenase Tet1 is highly expressed in the epiblast and yet continues to regulate lineage specification during gastrulation when its expression is diminished. Here, we show how Tet1 plays a pivotal role upstream of germ layer lineage bifurcation. During the transition from naive pluripotency to lineage priming, a global reconfiguration re-distributes Tet1 from Oct4 co-bound promoters to distal regulatory elements at lineage differentiation genes which are distinct from high-affinity sites engaged by Oct4. An altered chromatin landscape in Tet1-deficient primed epiblast-like cells is associated with enhanced Oct4 expression and binding to Nodal and Wnt target genes, resulting in collaborative signals that enhance mesendodermal and inhibit neuroectodermal gene expression during lineage segregation. A permissive role for Tet1 in neural fate induction involves Zic2-dependent engagement at neural target genes at lineage priming, is dependent on the signaling environment during gastrulation and impacts neural tube closure at post-gastrulation. Our findings provide mechanistic information for epigenetic integration of pluripotency and signal-induced differentiation cues.

2020-03-02 | GSE144867 | GEO

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

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 characterised Smad2/3-deificient embryonic stem cells (ESCs). We found that Smad2/3 double-knockout ESCs induced to form epiblast-like cells (EpiLCs) display changes in naïve and primed pluripotency marker gene expression, associated with the disruption of Oct4-bound distal regulatory element. 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 lakers 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.

2018-08-14 | GSE110163 | GEO

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

2018-08-14 | GSE110162 | GEO

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

2018-08-14 | GSE110058 | GEO

Maintenance of pluripotency signature in the entire ectoderm enables potential for neural crest formation [scRNASeq]

Project description:The ability of the pluripotent epiblast to contribute progeny to all three germ layers is thought to be lost after gastrulation. The later-forming neural crest (NC) rises from ectoderm and it remains poorly understood how its exceptionally high stem-cell potential to generate mesodermal- and endodermal-like cells is obtained. We monitored transcriptional changes from gastrulation to neurulation using single-cell-Multiplex-Spatial-Transcriptomics (scMST) complemented with RNA-sequencing. Here we show maintenance of pluripotency-signature (Nanog/Oct4-PouV/Klf4-positive) in undecided pan-ectodermal stem-cells spanning the entire ectoderm late during neurulation with ectodermal patterning completed only at the end of neurulation when the pluripotency-signature becomes restricted to NC, challenging our understanding of gastrulation. Furthermore, broad ectodermal pluripotency-signature is found at all axial levels unrelated to the NC lineage the cells later commit to, suggesting a general role in stemness enhancement and proposing a mechanism by which the NC acquires its ability to form derivatives beyond “ectodermal-capacity” in chick and mouse embryos.

2023-03-02 | GSE221188 | GEO

Maintenance of pluripotency signature in the entire ectoderm enables potential for neural crest formation [bulk_RNASeq]

2023-03-02 | GSE221125 | GEO

Maintenance of pluripotency signature in the entire ectoderm enables potential for neural crest formation

Project description:The ability of the pluripotent epiblast to contribute progeny to all three germ layers is thought to be lost after gastrulation. The later-forming neural crest (NC) rises from ectoderm and it remains poorly understood how its exceptionally high stem-cell potential to generate mesodermal- and endodermal-like cells is obtained. We monitored transcriptional changes from gastrulation to neurulation using single-cell-Multiplex-Spatial-Transcriptomics (scMST) complemented with RNA-sequencing. Unexpectedly, we find maintenance of undecided Nanog/Oct4-PouV/Klf4-positive pluripotent-like pan-ectodermal stem-cells spanning the entire ectoderm late in the neurulation process with ectodermal patterning completed only at the end of neurulation when pluripotency becomes restricted to NC, challenging our understanding of gastrulation. Furthermore, broad ectodermal pluripotency is found at all axial levels unrelated to the NC lineage the cells later commit to, suggesting a general role in stemness enhancement and proposing a mechanism by which the NC acquires its ability to form derivatives beyond “ectodermal-capacity” in chick and mouse embryos.

2023-08-28 | GSE232432 | GEO

Epigenetic regulation and transcriptional repression by Tet1 in the early post-implantation mouse embryo: Methylation data.

Project description:The mammalian TET dioxygenases contribute to global waves of DNA demethylation in the zygote and in primordial germ cells, but their involvement during de novo DNA methylation at peri/post-implantation development is unknown. Here, we show novel physiological functions of Tet1 in the pre-primitive streak stage mouse embryo, where it is expressed not only in the primed-state epiblast, but also in the extra-embryonic ectoderm. In the epiblast, Tet1 contributes to DNA methylation patterning, which indirectly results in dominant transcriptional repression involving a Jumonji-family gene Jmjd8. In the extra-embryonic ectoderm, Tet1 suppresses expression of metabolic genes involved in oxidative phosphorylation. These lineage-specific gene repressive functions, involving distinct modes of regulation by DNA methylation, counteract precocious differentiation of the embryo prior to the onset of gastrulation. Such dysregulation in the absence of Tet1 are surprisingly tolerated in an inbred strain but results in full embryonic lethality in non-inbred mice, thus implicating a complex but essential role of Tet1 in normal gestational development.

2017-05-15 | E-MTAB-4581 | biostudies-arrayexpress

Epigenetic regulation and transcriptional repression by Tet1 in the early post-implantation mouse embryo: ChIP seq

2017-05-15 | E-MTAB-5562 | biostudies-arrayexpress

Epigenetic regulation and transcriptional repression by Tet1 in the early post-implantation mouse embryo: WG Bisulfite sequencing

2017-05-15 | E-MTAB-5568 | biostudies-arrayexpress