ArticleStem cells (Dayton, Ohio)2014
Retinoic acid suppresses the canonical Wnt signaling pathway in embryonic stem cells and activates the noncanonical Wnt signaling pathway.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Retinoic acid as a stage-specific modulator of hematopoietic lineage fate from human pluripotent stem cells.Cell communication and signaling : CCS · 2026Article
- Dynamic cell fate transitions during morphallactic regeneration.Nature communications · 2026Article
- Article
- Retinoic Acid Receptor γ Activity Plays a Critical Role in Regulating Early Mouse Gastruloid Development.International journal of molecular sciences · 2026Article
- Vitamin A deficiency attenuates cardiac rupture inFrontiers in cardiovascular medicine · 2025Article
- WNT Signaling in Stem Cells: A Look into the Non-Canonical Pathway.Stem cell reviews and reports · 2024Review
- Wnt and BMP signalling direct anterior-posterior differentiation in aggregates of mouse embryonic stem cells.Biology open · 2023Article
- Review
- Gene-nutrient interactions that impact magnesium homeostasis increase risk for neural tube defects in mice exposed to dolutegravir.Frontiers in cell and developmental biology · 2023Article
- Retinoic acid effects on in vitro palatal fusion and WNT signaling.European journal of oral sciences · 2022Article
- Human milk oligosaccharide 2'-fucosyllactose promotes melanin degradation via the autophagic AMPK-ULK1 signaling axis.Scientific reports · 2022Article
- Dysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome.International journal of molecular sciences · 2022Article
- Signaling Pathways Impact on Induction of Corneal Epithelial-like Cells Derived from Human Wharton's Jelly Mesenchymal Stem Cells.International journal of molecular sciences · 2022Article
- Article
- Synthetic Retinoids Beyond Cancer Therapy.Annual review of pharmacology and toxicology · 2022Review
- Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma.BMC cancer · 2021Article
- Noncanonical Wnt Signaling Promotes Myofibroblast Differentiation in Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2021Article
- Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human β cell specification.Development (Cambridge, England) · 2020Article
- Cleft lip and cleft palate inDevelopment (Cambridge, England) · 2020Article
- Retinoic acid receptor α as a novel contributor to adrenal cortex structure and function through interactions with Wnt and Vegfa signalling.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Embryonic stem cells (ESCs) have both the ability to self-renew and to differentiate into various cell lineages. Retinoic acid (RA), a metabolite of Vitamin A, has a critical function in initiating lineage differentiation of ESCs through binding to the retinoic acid receptors. Additionally, the Wnt signaling pathway plays a role in pluripotency and differentiation, depending on the activation status of the canonical and noncanonical pathways. The activation of the canonical Wnt signaling pathway, which requires the nuclear accumulation of β-catenin and its interaction with Tcf1/Lef at Wnt response elements, is involved in ESC stemness maintenance. The noncanonical Wnt signaling pathway, through actions of Tcf3, can antagonize the canonical pathway. We show that RA activates the noncanonical Wnt signaling pathway, while concomitantly inhibiting the canonical pathway. RA increases the expression of ligands and receptors of the noncanonical Wnt pathway (Wnt 5a, 7a, Fzd2 and Fzd6), downstream signaling, and Tcf3 expression. RA reduces the phosphorylated β-catenin levels by fourfold, although total β-catenin levels do not change. We show that RA signaling increases the dissociation of Tcf1 and the association of Tcf3 at promoters of genes that regulate stemness (e.g., NR5A2, Lrh-1) or differentiation (e.g. Cyr61, Zic5). Knockdown of Tcf3 increases Lrh-1 transcript levels in mESCs and prevents the RA-associated, fourfold increase in Zic5, indicating that RA requires Tcf3 to effect changes in Zic5 levels. We demonstrate a novel role for RA in altering the activation of these two Wnt signaling pathways and show that Tcf3 mediates some actions of RA during differentiation.
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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.