Differential Nodal level promotes mesendoderm cell fate segregation mediated by chromatin organization
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ABSTRACT:
PROVIDER: PRJNA927004 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23210471.fastq.gz | Fastqsanger.gz | |||
| SRR23210472_1.fastq.gz | Fastqsanger.gz | |||
| SRR23210472_2.fastq.gz | Fastqsanger.gz | |||
| SRR23210473_1.fastq.gz | Fastqsanger.gz | |||
| SRR23210473_2.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: To investigate the mechanism of prechordal plate and anterior endoderm separation . Methods: Nodal injected explants (injected with 10pg ndr2 mRNA) constructed from lft1 mutants and ndr1 morphants were harvested at 6hpf. Libraries were prepared using Chromium Controller and Chromium Single Cell 3’Library & Gel Bead Kit v3 (10x Genomics, PN-1000075) according to the manufacturer’s protocol for 10000 cells recovery. For single-cell multiomics, zebrafish embryos at 6 hpf were harvested. Libraries were prepared using Chromium Next GEM Single Cell Multiome ATAC + Gene Expression Reagent Bundle (10x Genomics, 4 rxns PN-1000285) according to the manufacturer’s protocol for 10000 cells recovery. Results: A total of 10,614 single-cell transcriptomes and 4,335 multiomics were collected after stringent quality control measures. Conclusions: A slight bias in Nodal signaling promotes a differential chromatin structure between prechordal plate and endoderm, which drives a differential expression of those key regulators, such as gsc and ripply1 in these two cell lineages, and further regulates mesendoderm cell fate separation.
2023-01-28 | GSE223636 | GEO
Project description:Dissection of anterior mesendoderm segregation at single cell level in zebrafish
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Project description:TGF-β signaling is a central regulator of early development in metazoans, yet our understanding of the scope of TGF-β signaling’s downstream targets and associated physiological mechanisms in specifying developmentally appropriate cell fates is far from complete. Here, we found that a highly conserved, primitive-streak-specific micropeptide is a direct target of TGF-b/Nodal signaling. This transmembrane micropeptide (NEMEP) is essential for mesendoderm differentiation. Depletion of NEMEP impaired mesendoderm differentiation and caused a significant decrease in glucose uptake, while TGF-β signaling enhances glucose uptake in a NEMEP-dependent manner. Biochemically, we show that NEMEP promotes glucose uptake through its interactions with GLUT1/3. Thus, beyond expanding the scope of known TGF-β signaling targets in early development and showing that this target micropeptide augments the glucose uptake function of major glucose transporters during mesendoderm differentiation, our study provides a clear example for the direct functional impact of altered metabolism on cell fate determination in early embryogenesis.
2021-11-03 | GSE157073 | GEO
Project description:The TGF-β superfamily member Nodal triggers mesendoderm differentiation in embryonic stem (ES) cells. This transition however requires cooperating Wnt signaling inputs. Here we report that p53, a powerful tumor suppressor in adult tissues, orchestrates this cooperation. We show that p53, which is released from inhibition as mouse ES cells exit from pluripotency, acts as a direct inducer of Wnt3 expression. Wnt-activated Tcf3 then converges with Nodal-activated Smad transcriptional complexes on mesendoderm specification super-enhancers. p53 and its homolog p73 act redundantly in Wnt induction. When p53 and p73 are depleted, the ES cells fail to secrete autocrine Wnt ligands, Tcf and Nodal-activated Smads fail to bind to mesendoderm gene enhancers, and the cells adopt ectoderm rather than mesendoderm identity. Enforced Wnt3 expression or addition of Wnt3a rescues mesendoderm differentiation in p53/p73-depleted ES cells. Thus, independently of their established role as tumor suppressors that guard genome integrity in mature cells, p53 and p73 serve a primordial role in ES cell differentiation by driving a cooperation of Wnt and TGF-β transcriptional inputs on mesendoderm identity gene enhancers.
2017-01-06 | GSE70486 | GEO
Project description:We defined the genome-wide binding regions of Smad2/3 and Foxh1 at mid-gastrula stage Xenopus tropicalis embryos, at which Nodal signaling and Foxh1 are critical in mesendoderm specification program.
2014-11-07 | GSE53652 | GEO
Project description:Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node and mesendoderm. In contradiction to this drive towards cellular differentiation, the pathway also plays important roles in the maintenance of self-renewal and pluripotency in embryonic and epiblast stem cells. The molecular basis behind stem cell interpretation of Nodal/Activin signaling gradients and the undertaking of disparate cell fate decisions remains poorly understood. Here, we show that any perturbation of endogenous signaling levels in mouse ES cells leads to their exit from self renewal towards divergent differentiation programs. Increasing Nodal signals above basal levels by direct stimulation with Activin promotes differentiation towards the mesendodermal lineages while repression of signaling with the specific Nodal/Activin receptor inhibitor SB431542 induces trophectodermal differentiation. To address how quantitative Nodal/Activin signals are translated qualitatively into distinct cell fates decisions, we performed chromatin immunoprecipitation of phospho-Smad2 the primary downstream transcriptional factor of the Nodal/Activin pathway followed by massively parallel sequencing and show that phospho-Smad2 binds to and regulates distinct subsets of target genes in a dose-dependent manner. Crucially, Nodal/Activin signaling directly controls the Oct4 master regulator of pluripotency by graded phospho-Smad2 binding in the promoter region. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titrates self-renewal against alternative differentiation programs by direct regulation of distinct target gene subsets and Oct4 expression. Four biological replicates consisting of 4 different passages of E14TG2a ES cells at P20, P21, P23 and P24
2011-06-30 | E-GEOD-23239 | biostudies-arrayexpress
Project description:Genome/chromosome organization is highly ordered and controls nuclear events. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosome organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres. Inhibition of the Cnd2-TBP interaction disrupts condensin localization across the genome and the proper assembly of mitotic chromosomes, leading to severe defects in chromosome segregation and eventually causing cellular lethality. We propose that the Cnd2-TBP interaction coordinates transcription with chromosomal architecture by linking dispersed gene loci with centromeres. This chromosome arrangement can contribute to the efficient transmission of physical force at the kinetochore to chromosomal arms, thereby supporting the fidelity of chromosome segregation. Genome-wide distributions of condensin and Pol III factors in fission yeast.
2015-08-12 | E-GEOD-60273 | biostudies-arrayexpress
Project description:ES cells are differentiated into mesenderm cell linage by Activin A treatment. During this differentaition, gene expression profile of ES cells, day 4 mesendoderm cell, day 5 mesendoderm cells and mesoderm cells are examined.
2009-06-12 | E-MEXP-1672 | biostudies-arrayexpress
Project description:TGF-β/Nodal signaling boosts glucose uptake during mesendoderm differentiation by inducing a transmembrane micropeptide
| PRJNA660018 | ENA
Project description:Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node and mesendoderm. In contradiction to this drive towards cellular differentiation, the pathway also plays important roles in the maintenance of self-renewal and pluripotency in embryonic and epiblast stem cells. The molecular basis behind stem cell interpretation of Nodal/Activin signaling gradients and the undertaking of disparate cell fate decisions remains poorly understood. Here, we show that any perturbation of endogenous signaling levels in mouse ES cells leads to their exit from self renewal towards divergent differentiation programs. Increasing Nodal signals above basal levels by direct stimulation with Activin promotes differentiation towards the mesendodermal lineages while repression of signaling with the specific Nodal/Activin receptor inhibitor SB431542 induces trophectodermal differentiation. To address how quantitative Nodal/Activin signals are translated qualitatively into distinct cell fates decisions, we performed chromatin immunoprecipitation of phospho-Smad2 the primary downstream transcriptional factor of the Nodal/Activin pathway followed by massively parallel sequencing and show that phospho-Smad2 binds to and regulates distinct subsets of target genes in a dose-dependent manner. Crucially, Nodal/Activin signaling directly controls the Oct4 master regulator of pluripotency by graded phospho-Smad2 binding in the promoter region. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titrates self-renewal against alternative differentiation programs by direct regulation of distinct target gene subsets and Oct4 expression.
2011-06-30 | GSE23239 | GEO