TGF-β/Nodal signaling boosts glucose uptake during mesendoderm differentiation by inducing a transmembrane micropeptide
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ABSTRACT:
PROVIDER: PRJNA660018 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12540680_1.fastq.gz | Fastqsanger.gz | |||
| SRR12540680_2.fastq.gz | Fastqsanger.gz | |||
| SRR12540681_1.fastq.gz | Fastqsanger.gz | |||
| SRR12540681_2.fastq.gz | Fastqsanger.gz | |||
| SRR12540682_1.fastq.gz | Fastqsanger.gz |
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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: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: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:Differential Nodal level promotes mesendoderm cell fate segregation mediated by chromatin organization
| PRJNA927004 | ENA
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: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 family proteins including Nodal are known as central regulators of early development in metazoans, yet our understanding of the scope of Nodal signaling's downstream targets and associated physiological mechanisms in specifying developmentally appropriate cell fates is far from complete. Here, we identified a highly conserved, transmembrane micropeptide-NEMEP-as a direct target of Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells (mESCs), and this micropeptide is essential for mesendoderm differentiation. We showed that NEMEP interacts with the glucose transporters GLUT1/GLUT3 and promotes glucose uptake likely through these interactions. Thus, beyond expanding the scope of known Nodal signaling targets in early development and showing that this target micropeptide augments the glucose uptake during mesendoderm differentiation, our study provides a clear example for the direct functional impact of altered glucose metabolism on cell fate determination.
| S-EPMC9271079 | biostudies-literature
Project description:Maternally expressed proteins function in vertebrates to establish the major body axes of the embryo, and to establish a pre-pattern that sets the stage for later acting zygotic signals. This pre-pattern drives the propensity of Xenopus animal cap cells to adopt neural fates under various experimental conditions. Previous studies found that the maternally expressed transcription factor, encoded by the Xenopus achaete-scute like gene ascl1, is enriched at the animal pole. Asc1l is a bHLH protein involved in neural development, but its maternal function has not been studied. In this study, we have performed a series of gain and loss of function experiments on maternal ascl1, and present three novel findings. First, Ascl1 is a repressor of mesendoderm induced by VegT, but not of Nodal induced mesendoderm. Secondly, a previously uncharacterized N-terminal domain of Ascl1 interacts with HDAC1 to inhibit mesendoderm gene expression. This N-terminal domain is dispensable for its neurogenic function, indicating that Ascl1 has acts by different mechanisms at different times. Ascl1-mediated repression of mesendoderm genes was dependent on HDAC activity and accompanied by histone deacetylation in the promoter regions of VegT targets. Finally, maternal Ascl1 is required for animal cap cells to retain their competence to adopt neural fates. These results establish maternal Asc1l as a key factor in establishing the pre-pattern of the early embryo, acting in opposition to VegT and biasing the animal pole to adopt neural fates. The data presented here significantly extend our understanding of early embryonic pattern formation. Examination of genes expression in control (cMO) and Ascl1 MO knockdown (AMOs) embryos by deep sequencing.
2016-01-16 | E-GEOD-76915 | biostudies-arrayexpress
Project description:TRIM33 is a chromatin reader required for mesendoderm differentiation upon activation of Nodal signaling. But, its role in mESCs is still elusive. Here, we found that TRIM33 co-localizes with promyelocytic leukemia nuclear bodies (PML NBs) specifically in mESCs to mediate Nodal signaling-directed transcription of Lefty1/2. We showed that TRIM33 puncta formation in mESCs depends on PML and specific assembly of PML NBs. Moreover, TRIM33 and PML co-regulate Lefty1/2 expression in mESCs. In addition, both PML and mESCs-specific PML NBs are required for TRIM33 recruitment at Lefty1/2 loci. Remarkably, PML NBs directly associate with the Lefty1/2 loci in mESCs. Finally, a TurboID proximity labeling experiment confirmed that TRIM33 is highly enriched in the mESCs-specific PML NBs. Thus, our study provides the mechanistic insight about TRIM33 condensate in regulating Nodal signaling-directed transcription in mESCs, it also reveals that PML NBs recruit distinct sets of client proteins in cell context dependent manner.
2022-12-08 | GSE199738 | GEO
Project description:During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.
| S-EPMC3928293 | biostudies-literature