Most cited article - PubMed ID 32985604
12-O-Tetradecanoylphorbol-13-acetate increases cardiomyogenesis through PKC/ERK signaling
Dual specificity phosphatase 7 (DUSP7) is a protein belonging to a broad group of phosphatases that can dephosphorylate phosphoserine/phosphothreonine as well as phosphotyrosine residues within the same substrate. DUSP7 has been linked to the negative regulation of mitogen activated protein kinases (MAPK), and in particular to the regulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). MAPKs play an important role in embryonic development, where their duration, magnitude, and spatiotemporal activity must be strictly controlled by other proteins, among others by DUSPs. In this study, we focused on the effect of DUSP7 depletion on the in vitro differentiation of mouse embryonic stem (ES) cells. We showed that even though DUSP7 knock-out ES cells do retain some of their basic characteristics, when it comes to differentiation, they preferentially differentiate towards neural cells, while the formation of early cardiac mesoderm is repressed. Therefore, our data indicate that DUSP7 is necessary for the correct formation of neuroectoderm and cardiac mesoderm during the in vitro differentiation of ES cells.
- MeSH
- Dual Specificity Phosphatase 1 metabolism MeSH
- Dual-Specificity Phosphatases genetics metabolism MeSH
- Phosphoserine MeSH
- Phosphothreonine MeSH
- Phosphotyrosine MeSH
- Mesoderm metabolism MeSH
- Mitogen-Activated Protein Kinases metabolism MeSH
- Mouse Embryonic Stem Cells * metabolism MeSH
- Mice MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Dusp7 protein, mouse MeSH Browser
- Dual Specificity Phosphatase 1 MeSH
- Dual-Specificity Phosphatases MeSH
- Phosphoserine MeSH
- Phosphothreonine MeSH
- Phosphotyrosine MeSH
- Mitogen-Activated Protein Kinases MeSH
Organic semiconductors are constantly gaining interest in regenerative medicine. Their tunable physico-chemical properties, including electrical conductivity, are very promising for the control of stem-cell differentiation. However, their use for combined material-based and electrical stimulation remains largely underexplored. Therefore, we carried out a study on whether a platform based on the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) can be beneficial to the differentiation of mouse embryonic stem cells (mESCs). The platform was prepared using the layout of a standard 24-well cell-culture plate. Polyethylene naphthalate foil served as the substrate for the preparation of interdigitated gold electrodes by physical vapor deposition. The PEDOT:PSS pattern was fabricated by precise screen printing over the gold electrodes. The PEDOT:PSS platform was able to produce higher electrical current with the pulsed-direct-current (DC) electrostimulation mode (1 Hz, 200 mV/mm, 100 ms pulse duration) compared to plain gold electrodes. There was a dominant capacitive component. In proof-of-concept experiments, mESCs were able to respond to such electrostimulation by membrane depolarization and elevation of cytosolic calcium. Further, the PEDOT:PSS platform was able to upregulate cardiomyogenesis and potentially inhibit early neurogenesis per se with minor contribution of electrostimulation. Hence, the present work highlights the large potential of PEDOT:PSS in regenerative medicine.
- Keywords
- PEDOT:PSS, conductive polymer, electrostimulation, embryonic stem cells, screen print,
- MeSH
- Bridged Bicyclo Compounds, Heterocyclic chemistry MeSH
- Cell Differentiation * MeSH
- Cell Culture Techniques MeSH
- Electric Conductivity * MeSH
- Electrodes MeSH
- Mouse Embryonic Stem Cells cytology drug effects MeSH
- Mice MeSH
- Polymers chemistry pharmacology MeSH
- Polystyrenes chemistry MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Bridged Bicyclo Compounds, Heterocyclic MeSH
- poly(3,4-ethylene dioxythiophene) MeSH Browser
- Polymers MeSH
- polystyrene sulfonic acid MeSH Browser
- Polystyrenes MeSH
RNF43 is an E3 ubiquitin ligase and known negative regulator of WNT/β-catenin signaling. We demonstrate that RNF43 is also a regulator of noncanonical WNT5A-induced signaling in human cells. Analysis of the RNF43 interactome using BioID and immunoprecipitation showed that RNF43 can interact with the core receptor complex components dedicated to the noncanonical Wnt pathway such as ROR1, ROR2, VANGL1, and VANGL2. RNF43 triggers VANGL2 ubiquitination and proteasomal degradation and clathrin-dependent internalization of ROR1 receptor and inhibits ROR2 activation. These activities of RNF43 are physiologically relevant and block pro-metastatic WNT5A signaling in melanoma. RNF43 inhibits responses to WNT5A, which results in the suppression of invasive properties of melanoma cells. Furthermore, RNF43 prevented WNT5A-assisted development of resistance to BRAF V600E and MEK inhibitors. Next, RNF43 acted as melanoma suppressor and improved response to targeted therapies in vivo. In line with these findings, RNF43 expression decreases during melanoma progression and RNF43-low patients have a worse prognosis. We conclude that RNF43 is a newly discovered negative regulator of WNT5A-mediated biological responses that desensitizes cells to WNT5A.
- Keywords
- BRAF V600E, RNF43, ROR1, VANGL1, WNT5A, cancer biology, cell biology, human, melanoma, mouse,
- MeSH
- Neoplasm Invasiveness genetics MeSH
- Melanoma * genetics pathology prevention & control MeSH
- Mice, Inbred NOD MeSH
- Mice MeSH
- Wnt-5a Protein genetics metabolism MeSH
- Signal Transduction * MeSH
- Ubiquitin-Protein Ligases genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Wnt-5a Protein MeSH
- RNF43 protein, human MeSH Browser
- Ubiquitin-Protein Ligases MeSH
- WNT5A protein, human MeSH Browser