ArticleProceedings of the National Academy of Sciences of the United States of America2016
Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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The trial behind it
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
78 citing papers in PubMed, 117 citations in OpenAlex.
- 14-Deoxy-11,12-didehydroandrographolide Promotes Ex Vivo Expansion of Umbilical Cord Blood Stem Cells through Stemness-Related Gene Regulation.ACS omega · 2026Article
- Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness.Experimental & molecular medicine · 2026Review
- The Yin-Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2026Article
- Advances and Applications of Spatial Proteomics: From Organellar Maps to Clinical Translation.Chembiochem : a European journal of chemical biology · 2026Review
- Acetylation of lysine 49 on Ctnnb1 drives naïve pluripotency in murine stem cells by modulating Nanog function.PNAS nexus · 2025Article
- Orientin Reverses Premature Senescence in Equine Adipose Stromal Cells Affected by Equine Metabolic Syndrome Through Oxidative Stress Modulation.International journal of molecular sciences · 2025Article
- Wnt Inhibition Safeguards Porcine Embryonic Stem Cells From the Acquisition of Extraembryonic Endoderm Cell Fates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DGCR8 haploinsufficiency leads to primate-specific RNA dysregulation and pluripotency defects.Nucleic acids research · 2025Article
- A comprehensive analysis of induced pluripotent stem cell (iPSC) production and applications.Frontiers in cell and developmental biology · 2025Review
- The Wnt pathway induces a naïve-like subpopulation in primed stem cells, while NME7AB leads to a homogeneous naïve-like population.PloS one · 2025Article
- Pluripotency genes of mammals: a network at work.Frontiers in bioengineering and biotechnology · 2025Review
- Arp2/3 complex activity enables nuclear YAP for naïve pluripotency of human embryonic stem cells.eLife · 2024Article
- Single cell spatial biology over developmental time can decipher pediatric brain pathologies.Neurobiology of disease · 2024Review
- MAST4 regulates stem cell maintenance with DLX3 for epithelial development and amelogenesis.Experimental & molecular medicine · 2024Article
- Trisomy 12 compromises the mesendodermal differentiation propensity of human pluripotent stem cells.In vitro cellular & developmental biology. Animal · 2024Article
- The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.Genes & diseases · 2024Review
- The SWI/SNF ATP-dependent chromatin remodeling complex in cell lineage priming and early development.Biochemical Society transactions · 2024Review
- Exploring Heparan Sulfate Proteoglycans as Mediators of Human Mesenchymal Stem Cell Neurogenesis.Cellular and molecular neurobiology · 2024Review
- Article
- BRD9-mediated control of the TGF-β/Activin/Nodal pathway regulates self-renewal and differentiation of human embryonic stem cells and progression of cancer cells.Nucleic acids research · 2023Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
In both mice and humans, pluripotent stem cells (PSCs) exist in at least two distinct states of pluripotency, known as the naïve and primed states. Our understanding of the intrinsic and extrinsic factors that enable PSCs to self-renew and to transition between different pluripotent states is important for understanding early development. In mouse embryonic stem cells (mESCs), Wnt proteins stimulate mESC self-renewal and support the naïve state. In human embryonic stem cells (hESCs), Wnt/β-catenin signaling is active in naïve-state hESCs and is reduced or absent in primed-state hESCs. However, the role of Wnt/β-catenin signaling in naïve hESCs remains largely unknown. Here, we demonstrate that inhibition of the secretion of Wnts or inhibition of the stabilization of β-catenin in naïve hESCs reduces cell proliferation and colony formation. Moreover, we show that addition of recombinant Wnt3a partially rescues cell proliferation in naïve hESCs caused by inhibition of Wnt secretion. Notably, inhibition of Wnt/β-catenin signaling in naïve hESCs did not cause differentiation. Instead, it induced primed hESC-like proteomic and metabolic profiles. Thus, our results suggest that naïve hESCs secrete Wnts that activate autocrine or paracrine Wnt/β-catenin signaling to promote efficient self-renewal and inhibit the transition to the primed state.
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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.