ArticleNature communications2024
A stepwise mode of TGFβ-SMAD signaling and DNA methylation regulates naïve-to-primed pluripotency and differentiation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- PCBP1 orchestrates amino acid metabolism burst during the naïve-to-primed pluripotency transition.Stem cell reports · 2026Article
- Transcriptional Bursting in Pluripotent Stem Cells.Biology · 2026Review
- Recent advances in TGF-β signaling: insights into regulation, pathophysiological function, and clinical translation.Cell regeneration (London, England) · 2026Article
- TGF-β1 Promotes the Recovery of Dorsal Root Ganglion Neurons from Cisplatin-Induced Injury Through Smad4-Dependent Mechanism.Current issues in molecular biology · 2026Article
- Stage- and cluster-specific regulation of chondrogenic gene programs by Sox9 in mouse embryonic limb buds.iScience · 2026Article
- Post-replicative chromatin accessibility predicts cell fate change.Stem cell reports · 2026Article
- Epigenetic editing of marine medaka (Zoological research · 2026Article
- Molecular time machines unleashed: small-molecule-driven reprogramming to reverse the senescence.Stem cells translational medicine · 2026Review
- Concrete Structure Inspired 3D-Printed Framework Mechanically Reinforced Zwitterionic Hydrogel for Efficient Postoperative Abdominal Adhesion Prevention.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- BMDx2: A Tool for Integrating Toxicogenomics-Based Dose-Dependency Analysis and AOP-Based Mechanistic Insights.Small methods · 2025Article
- Systematic evaluation of porcine platelet lysate as a fetal bovine serum substitute: enhancing cell proliferation, maintaining differentiation potential, and ensuring immunophenotypic stability.Stem cell research & therapy · 2025Article
- 3D alveolar organoid drug screening model for targeting TGF-β1 in pulmonary fibrosis.Biochemistry and biophysics reports · 2025Article
- Advances in the regulation of macrophage polarization by the tumor microenvironment.Discover oncology · 2025Review
- Energy Metabolism and Stemness and the Role of Lauric Acid in Reversing 5-Fluorouracil Resistance in Colorectal Cancer Cells.International journal of molecular sciences · 2025Article
- Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025Review
- Pathological Mechanisms of Radiation-Induced Lung Injury and Novel Nano-Drug Delivery Therapeutic Strategies.International journal of nanomedicine · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The formation of transcription regulatory complexes by the association of Smad4 with Smad2 and Smad3 (Smad2/3) is crucial in the canonical TGFβ pathway. Although the central requirement of Smad4 as a common mediator is emphasized in regulating TGFβ signaling, it is not obligatory for all responses. The role of Smad2/3 independently of Smad4 remains understudied. Here, we introduce a stepwise paradigm in which Smad2/3 regulate the lineage priming and differentiation of mouse embryonic stem cells (mESCs) by collaboration with different effectors. During the naïve-to-primed transition, Smad2/3 upregulate DNA methyltransferase 3b (Dnmt3b), which establishes the proper DNA methylation patterns and, in turn, enables Smad2/3 binding to the hypomethylated centers of promoters and enhancers of epiblast marker genes. Consequently, in the absence of Smad2/3, Smad4 alone cannot initiate epiblast-specific gene transcription. When primed epiblast cells begin to differentiate, Dnmt3b becomes less actively engaged in global genome methylation, and Smad4 takes over the baton in this relay race, forming a complex with Smad2/3 to support mesendoderm induction. Thus, mESCs lacking Smad4 can undergo the priming process but struggle with the downstream differentiation. This work sheds light on the intricate mechanisms underlying TGFβ signaling and its role in cellular processes.
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