Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA288818 | ENA |
REPOSITORIES: ENA
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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: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:To recognize the influnence of WNT signaling on fibroblasts differentiation first we analyzed transformation of human cardiac fibroblasts caused by TGF-β signaling. Differential gene expression analysis demonstrated that cardiac fibroblasts 72h after treatment with TGF-β showed deregulated expression of 313 genes. We also observed that stimulation with WNT3a resulted in deregulation of 124 genes in TGF-β-treated fibroblasts and in contrast to profound effect of WNT3a on fibroblasts differentiation, treatment with WNT5a upregulated expression of only 2 and downregulated 21 genes in TGF-β-activated cells.
2021-08-08 | GSE181575 | GEO
Project description:In this project we evaluated the proteomic profiling with TGF-β stimuli at 24h in a CRISPR-Cas9 model for ALMS1 gene in hTERT-BJ-5ta cells. Proteomic results showed a majority inhibition of downstream regulated pathways by the TGF-β, associating the protein coding genes (PCG) with processes like TGF- β matrix regulation, epithelial mesenchymal transition (EMT), PI3K/AKT or P53. In conclusion, seems that the depletion of ALMS1 could be inhibiting the signals transduction through the TGF -β and the routes regulated downstream.
2024-01-26 | PXD035708 | Pride
Project description:Idiopathic pulmonary fibrosis (IPF) is characterized by devastating and progressive lung parenchymal fibrosis with poor prognosis. An aberrant recapitulation of lung developmental genes including transforming growth factor (TGF)-β and WNT has been widely implicated in the abnormal wound healing process following repetitive alveolar epithelial injury during IPF pathogenesis. Extracellular vesicles (EVs) including exosomes and microvesicles have been shown to carry various bioactive molecules and are involved in a variety of physiological and pathological processes. Here, we demonstrate that human bronchial epithelial cell-derived EVs (HBEC EVs) inhibited TGF-β-induced both myofibroblast differentiation and lung epithelial cellular senescence through attenuating WNT signaling. To ask how HBEC-EVs inhibited TGF-β-induced both myofibroblast differentiation and lung epithelial cellular senescence through attenuating WNT signaling, miRNA RNA-seq of HBEC-EVs was performed.
2021-08-18 | GSE158623 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is characterized by devastating and progressive lung parenchymal fibrosis with poor prognosis. An aberrant recapitulation of lung developmental genes including transforming growth factor (TGF)-β and WNT has been widely implicated in the abnormal wound healing process following repetitive alveolar epithelial injury during IPF pathogenesis. Extracellular vesicles (EVs) including exosomes and microvesicles have been shown to carry various bioactive molecules and are involved in a variety of physiological and pathological processes. Here, we demonstrate that human bronchial epithelial cell-derived EVs (HBEC EVs) inhibited TGF-β-induced both myofibroblast differentiation and lung epithelial cellular senescence through attenuating WNT signaling. To ask how HBEC-EVs inhibited TGF-β-induced both myofibroblast differentiation and lung epithelial cellular senescence through attenuating WNT signaling, miRNA RNA-seq of HBEC-EVs was performed.
2021-08-18 | GSE156572 | GEO
Project description:Activin and Wnt signaling are necessary and sufficient for mesendoderm (ME) differentiation of human embryonic stem cells (hESCs). In this study, we report that during the Activin and Wnt induced ME differentiation, Activin/Smad2 induces decrease of the repressive histone modification H3K27me3 by promoting proteasome-dependent degradation of EZH2. As a result, recruitment of the forkhead protein FOXH1 on open chromatin regions integrates the signals of Activin/Smad2 and Wnt/β-catenin to activate the expression of the ME genes including HAS2 and ALDH3A2. Knockdown of HAS2 and ALDH3A2 greatly attenuates ME differentiation. These findings unveil a pathway from extracellular signals to epigenetic modification-mediated gene activation during ME commitment.
2018-09-29 | GSE113047 | GEO
Project description:Wnt/beta-catenin signaling is involved in various aspects of skeletal muscle development and regeneration. Using C2C12 cells, we examined intracellular signaling and gene transcription during myoblast proliferation and differentiation. The results of the present studies suggest that Wnt signaling is interacting with TGF-beta superfamily signaling through Smad activation. Single analysis for each condition (proliferating C2C12 cells, differentiating C2C12 cells, proliferating Wnt4-overexpressing C2C12 subline cells).
2013-06-21 | E-GEOD-40456 | biostudies-arrayexpress
Project description:The mechanistic target of rapamycin complex 2 (mTORC2) is essential for embryonic development but the underlying molecular mechanisms remain unclear. Here we show that disruption of mTORC2 in human embryonic stem cells (hESCs) considerably alters the balance of Rho/Rac signaling and reduces cell adhesion. Although these changes have no clear effect on their self-renewal and the expression of pluripotent markers, they significantly impede BMP-induced activation of canonical WNT genes, leading to impaired mesendoderm differentiation. Direct activation of the downstream WNT pathway by inhibiting GSK3 dramatically improves mesendoderm differentiation in mTORC2-deficient hESCs. Our studies uncover a new mechanism by which mTORC2 regulates cell fate determination and link the intercellular contacts with the activation of WNT genes.
2023-11-06 | GSE243723 | GEO
Project description:To assess and distinguish the molecular role of PCGF6 in the self-renewal and early differentiation of PSCs, we established PCGF6-knockout PSCs. Although the absence of PCGF6 could maintain self-renewal and colony-formation capacity, it induced abnormal early differentiation in PSCs. PCGF6 deficiency in PSCs promoted the development of mesendoderm, and impaired the development of neuroectoderm during differentiation process in vitro. RNA-seq and ChIP-seq experiments revealed that PCGF6 plays different roles in distinct lineage specification. On the one hand, PCGF6 worked as a transcription activator that maintain early neuroectoderm differentiation by regulating the expression of SOX2. On the other hand, PCGF6 resists skewed differentiation toward mesendoderm through the PRC1-dependent inhibition of WNT/β-catenin signaling pathways.
2022-07-16 | GSE173690 | GEO