ArticleCell stem cell2012
Signaling network crosstalk in human pluripotent cells: a Smad2/3-regulated switch that controls the balance between self-renewal and differentiation.
Article in Cell stem cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
193 citing papers in PubMed, 359 citations in OpenAlex.
- Chemical Screening Identifies Danofloxacin as a Self-Renewal Agonist of Embryonic Stem Cells through Alleviation of HDAC1-Mediated Deacetylation of Tert and Prdm10.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TGFβ-dependent upregulation of OCIAD2 is essential for epithelial-to-mesenchymal transition during mesendoderm differentiation.Stem cell reports · 2026Article
- Mechanosensitive phosphorylation of NFATC4 at S213/S217 drives fibroblast-to-myofibroblast transition and fibrosis.The Journal of clinical investigation · 2026Article
- Oxidative Phosphorylation and Fatty Acid Oxidation Are Central to Mitochondrial Metabolism Rewiring in CML Stem/Progenitor Cell Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- ERK-Mediated Phosphorylation of YAP Defines a Noncanonical FGF Signaling Mechanism in Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Impaired Neurosphere Formation as a Functional Readout of Aberrant EGFR Signaling Kinetics in Olfactory Neural Progenitors From Patients With Schizophrenia.Cell biology international · 2026Article
- From chemically defined hiPSCs to self-organizing cardiac organoids: current strategies guided by developmental signaling.Stem cell research & therapy · 2026Review
- Dependence of cell fate potential and cadherin switching on the coordinate within the primitive streak during differentiation of human pluripotent stem cells.Development (Cambridge, England) · 2026Article
- TGFβ-activated PDHB promotes mitochondrial pyruvate metabolism and contributes to human endoderm differentiation via ATP-dependent BRG1.Nature communications · 2026Article
- The Evolutionarily Conserved TPM1 Super-Enhancer Drives Skeletal Muscle Regeneration via Mechanotransduction Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adjusting PSC culture for neural organoid generation.Stem cell reports · 2026Article
- A human epiblast model reveals dynamic TGFβ-mediated control of epithelial identity during mammalian epiblast development.Nature cell biology · 2026Article
- Building a human pluripotent stem cell-based gonadal niche: improving in vitro systems with in vivo insights.Human reproduction update · 2025Review
- Genome-Wide Silencer Screening Reveals Key Silencer Modulating Reprogramming Efficiency in Mouse Induced Pluripotent Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm.American journal of physiology. Heart and circulatory physiology · 2025Article
- EIF3D safeguards the homeostasis of key signaling pathways in human primed pluripotency.Science advances · 2025Article
- ETVs dictate hPSC differentiation by tuning biophysical properties.Nature communications · 2025Article
- OCT4 translationally promotes AKT signaling as an RNA-binding protein in stressed pluripotent stem cells.Stem cell research & therapy · 2025Article
- Wnt Signaling Pathway in Tumor Biology.Genes · 2024Review
- The IMPDH cytoophidium couples metabolism and fetal development in mice.Cellular and molecular life sciences : CMLS · 2024Article
133 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A general mechanism for how intracellular signaling pathways in human pluripotent cells are coordinated and how they maintain self-renewal remain to be elucidated. In this report, we describe a signaling mechanism where PI3K/Akt activity maintains self-renewal by restraining prodifferentiation signaling through suppression of the Raf/Mek/Erk and canonical Wnt signaling pathways. When active, PI3K/Akt establishes conditions where Activin A/Smad2,3 performs a pro-self-renewal function by activating target genes, including Nanog. When PI3K/Akt signaling is low, Wnt effectors are activated and function in conjunction with Smad2,3 to promote differentiation. The switch in Smad2,3 activity after inactivation of PI3K/Akt requires the activation of canonical Wnt signaling by Erk, which targets Gsk3β. In sum, we define a signaling framework that converges on Smad2,3 and determines its ability to regulate the balance between alternative cell states. This signaling paradigm has far-reaching implications for cell fate decisions during early embryonic development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.