ArticlePloS one2016
CHIR99021 enhances Klf4 Expression through β-Catenin Signaling and miR-7a Regulation in J1 Mouse Embryonic Stem Cells.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Review
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- A small molecule strategy with forskolin and p38 inhibitor for serum-free muscle stem cell expansion.NPJ science of food · 2026Article
- Novel feeder-cell-free 3C system promotes the transition from primed to formative pluripotency, self-renewal, and germline differentiation in rabbit embryonic stem cellsFrontiers in cell and developmental biology · 2026Article
- CHIR99021 Enhances the Proliferation of Mouse Female Germline Stem Cells Via Modulating ERCC2.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- CHIR99021 Maintenance of the Cell Stemness by Regulating Cellular Iron Metabolism.Antioxidants (Basel, Switzerland) · 2023Article
- The concurrent stimulation of Wnt and FGF8 signaling induce differentiation of dental mesenchymal cells into odontoblast-like cells.Medical molecular morphology · 2022Article
- Regulation of NANOG and SOX2 expression by activin A and a canonical WNT agonist in bovine embryonic stem cells and blastocysts.Biology open · 2021Article
- 5-Aza-2'-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells.Molecules (Basel, Switzerland) · 2021Article
- Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin.Stem cell reports · 2020Article
- Canonical Wnt Pathway Controls mESC Self-Renewal Through Inhibition of Spontaneous Differentiation via β-Catenin/TCF/LEF Functions.Stem cell reports · 2020Article
- Characterization of Stem-like Circulating Tumor Cells in Pancreatic Cancer.Diagnostics (Basel, Switzerland) · 2020Article
- Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2.International journal of molecular sciences · 2019Article
- Negative Regulation of Kruppel-Like Factor 4 on microRNA-106a at Upstream Transcriptional Level and the Role in Gastric Cancer Metastasis.Digestive diseases and sciences · 2018Article
- Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity: Evidence From Mouse and Human Studies.Circulation · 2017Article
- Sevoflurane represses the self-renewal ability by regulating miR-7a,7b/Klf4 signalling pathway in mouse embryonic stem cells.Cell proliferation · 2016Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the mechanisms that regulate pluripotency of embryonic stem cells (ESCs) is important to ensure their safe clinical use. CHIR99021 (CHIR)-induced activation of Wnt/β-catenin signaling promotes self-renewal in mouse ESCs (mESCs). β-catenin functions individually or cooperates with transcription factors to activate stemness factors such as c-Myc, Esrrb, Pou5f1, and Nanog. However the relationship between the core pluripotent factor, Kruppel-like factor 4 (also known as GKLF or EZF) and Wnt/β-catenin signaling, remains ambiguous in J1 mESCs. DNA microarray analysis revealed that CHIR-treatment promoted pluripotency-maintaining transcription factors and repressed germ layer specification markers. CHIR also promoted genes related to the development of extracellular regions and the plasma membrane to maintain pluripotency of J1 mESCs. Among the CHIR-regulated genes, Klf4 has not been reported previously. We identified a novel cis element in the Klf4 gene that was activated by β-catenin in J1 mESCs. We determined that β-catenin interacted with this cis element, identifying Klf4 as a β-catenin target gene in this context. Moreover, several microRNAs that targeted the 3'-UTR of Klf4 mRNA were identified, with miR-7a being down-regulated by CHIR in a β-catenin-independent manner in J1 mESCs. These data collectively suggest that CHIR enhances Klf4 expression by repressing miR-7a expression or canonical Wnt pathway activation.
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