ArticlePloS one2010
REX-1 expression and p38 MAPK activation status can determine proliferation/differentiation fates in human mesenchymal stem cells.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 73 citations in OpenAlex.
- Identification of mesenchymal stem cells in perinodular fat and skin in Dupuytren's disease: a potential source of myofibroblasts with implications for pathogenesis and therapy.Stem cells and development · 2012Trial
- ZFP42 maintains stemness and rhythmic transcription in human epidermal stem and progenitor cells via CRY1.Communications biology · 2026Article
- Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications.Cell death & disease · 2025Review
- The Impact of IFN-γ Licensing on Mesenchymal Stromal Cells' Mediated Immunoregulation and HLA Class II Expression: Emerging Evidence from In Vitro Results.International journal of molecular sciences · 2025Article
- Hypoxic endometrial epithelial cell-derived microRNAs effectively regulate the regenerative properties of mesenchymal stromal cells.World journal of stem cells · 2025Article
- Establishment and characterization of a human juvenile bone marrow-derived mesenchymal stem/stromal cell line under advanced culture conditions for osteogenic differentiation.Frontiers in bioengineering and biotechnology · 2025Article
- A review on gold nanoparticles as an innovative therapeutic cue in bone tissue engineering: Prospects and future clinical applications.Materials today. Bio · 2024Article
- Emerging roles of mitochondrial functions and epigenetic changes in the modulation of stem cell fate.Cellular and molecular life sciences : CMLS · 2024Review
- Trends of regenerative tissue engineering for oral and maxillofacial reconstruction in veterinary medicine.Frontiers in veterinary science · 2024Review
- Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro.International journal of molecular sciences · 2023Article
- Pluripotent Stem Cells of Order Carnivora: Technical Perspective.International journal of molecular sciences · 2023Review
- Cancer Angiogenesis and Opportunity of Influence on Tumor by Changing Vascularization.Journal of personalized medicine · 2022Review
- Comparative characteristic study from bone marrow-derived mesenchymal stem cells.Journal of veterinary science · 2021Review
- Hypothermically Stored Adipose-Derived Mesenchymal Stromal Cell Alginate Bandages Facilitate Use of Paracrine Molecules for Corneal Wound Healing.International journal of molecular sciences · 2020Article
- Preconditioning of Adipose-Derived Mesenchymal Stem-Like Cells with Eugenol Potentiates Their Migration and Proliferation In Vitro and Therapeutic Abilities in Rat Hepatic Fibrosis.Molecules (Basel, Switzerland) · 2020Article
- 3D Culture of MSCs on a Gelatin Microsphere in a Dynamic Culture System Enhances Chondrogenesis.International journal of molecular sciences · 2020Article
- The Influence of Astaxanthin on the Proliferation of Adipose-derived Mesenchymal Stem Cells in Gelatin-Methacryloyl (GelMA) Hydrogels.Materials (Basel, Switzerland) · 2019Article
- Elevated level of mitochondrial reactive oxygen species via fatty acid β-oxidation in cancer stem cells promotes cancer metastasis by inducing epithelial-mesenchymal transition.Stem cell research & therapy · 2019Article
- Icariin induces cell differentiation and cell cycle arrest in mouse melanoma B16 cells via Erk1/2-p38-JNK-dependent pathway.Oncotarget · 2017Article
- The Role of Cellular Proliferation in Adipogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells.Stem cells and development · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundREX1/ZFP42 is a well-known embryonic stem cell (ESC) marker. However, the role of REX1, itself, is relatively unknown because the function of REX1 has only been reported in the differentiation of ESCs via STAT signaling pathways. Human mesenchymal stem cells (hMSCs) isolated from young tissues and cancer cells express REX1. METHODOLOGY/PRINCIPAL FINDING: Human umbilical cord blood-derived MSCs (hUCB-MSCs) and adipose tissue-derived MSCs (hAD-MSCs) strongly express REX1 and have a lower activation status of p38 MAPK, but bone marrow-derived MSCs (hBM-MSCs) have weak REX1 expression and higher activation of p38 MAPK. These results indicated that REX1 expression in hMSCs was positively correlated with proliferation rates but inversely correlated with the phosphorylation of p38 MAPK. In hUCB-MSCs, the roles of REX1 and p38 MAPK were investigated, and a knockdown study was performed using a lentiviral vector-based small hairpin RNA (shRNA). After REX1 knockdown, decreased cell proliferation was observed. In REX1 knocked-down hUCB-MSCs, the osteogenic differentiation ability deteriorated, but the adipogenic potential increased or was similar to that observed in the controls. The phosphorylation of p38 MAPK in hUCB-MSCs significantly increased after REX1 knockdown. After p38 MAPK inhibitor treatment, the cell growth in REX1 knocked-down hUCB-MSCs almost recovered, and the suppressed expression levels of CDK2 and CCND1 were also restored. The expression of MKK3, an upstream regulator of p38 MAPK, significantly increased in REX1 knocked-down hUCB-MSCs. The direct binding of REX1 to the MKK3 gene was confirmed by a chromatin immunoprecipitation (ChIP) assay. CONCLUSIONS/SIGNIFICANCE: These findings showed that REX1 regulates the proliferation/differentiation of hMSCs through the suppression of p38 MAPK signaling via the direct suppression of MKK3. Therefore, p38 MAPK and REX-1 status can determine the cell fate of adult stem cells (ASCs). These results were the first to show the role of REX1 in the proliferation/differentiation of ASCs.
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