ArticleCell communication and signaling : CCS2018
bFGF-mediated pluripotency maintenance in human induced pluripotent stem cells is associated with NRAS-MAPK signaling.
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- ERK-Mediated Phosphorylation of YAP Defines a Noncanonical FGF Signaling Mechanism in Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From chemically defined hiPSCs to self-organizing cardiac organoids: current strategies guided by developmental signaling.Stem cell research & therapy · 2026Review
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- NN15-017 promotes human pluripotent stem cell proliferation and generation.Regenerative therapy · 2025Article
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- FGF2 supports NANOG expression via pyruvate dehydrogenase-dependent histone acetylation under low oxygen conditions.Frontiers in cell and developmental biology · 2025Article
- Generation of bovine iPSCs from fetal fibroblasts for in vitro myogenesis and cultured meat.Frontiers in nutrition · 2025Article
- Lung-derived soluble factors support stemness/plasticity and metastatic behaviour of breast cancer cells via the FGF2-DACH1 axis.Clinical & experimental metastasis · 2024Article
- Canine induced pluripotent stem cells can be successfully maintained in weekend-free culture systems.The Journal of veterinary medical science · 2024Article
- Xiaozheng pill exerts an anti-mammary hyperplasia effect through Raf/ERK/ELK and HIF-1α/bFGF pathways.Journal of traditional and complementary medicine · 2023Article
- Profiling A-to-I RNA editing during mouse somatic reprogramming at the single-cell level.Heliyon · 2023Article
- The Role of ATP-Binding Cassette Proteins in Stem Cell Pluripotency.Biomedicines · 2023Review
- Molecular and cellular evidence for the impact of a hypertrophic cardiomyopathy-associated RAF1 variant on the structure and function of contractile machinery in bioartificial cardiac tissues.Communications biology · 2023Article
- Role of glycosphingolipid SSEA-3 and FGF2 in the stemness and lineage commitment of multilineage differentiating stress enduring (MUSE) cells.Cell proliferation · 2023Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Article
- Fibroblast growth factor 2 suppresses the expression of C-C motif chemokine 11 through the c-Jun N-terminal kinase pathway in human dental pulp-derived mesenchymal stem cells.Experimental and therapeutic medicine · 2021Article
- Sequential growth factor exposure of human Ad-MSCs improves chondrogenic differentiation in an osteochondral biphasic implant.Experimental and therapeutic medicine · 2021Article
- Accessory proteins of the RAS-MAPK pathway: moving from the side line to the front line.Communications biology · 2021Review
- Promotion of cancer cell stemness by Ras.Biochemical Society transactions · 2021Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman pluripotent stem cells (PSCs) open new windows for basic research and regenerative medicine due to their remarkable properties, i.e. their ability to self-renew indefinitely and being pluripotent. There are different, conflicting data related to the role of basic fibroblast growth factor (bFGF) in intracellular signal transduction and the regulation of pluripotency of PSCs. Here, we investigated the effect of bFGF and its downstream pathways in pluripotent vs. differentiated human induced (hi) PSCs.
methodsbFGF downstream signaling pathways were investigated in long-term culture of hiPSCs from pluripotent to differentiated state (withdrawing bFGF) using immunoblotting, immunocytochemistry and qPCR. Subcellular distribution of signaling components were investigated by simple fractionation and immunoblotting upon bFGF stimulation. Finally, RAS activity and RAS isoforms were studied using RAS assays both after short- and long-term culture in response to bFGF stimulation.
resultsOur results revealed that hiPSCs were differentiated into the ectoderm lineage upon withdrawing bFGF as an essential pluripotency mediator. Pluripotency markers OCT4, SOX2 and NANOG were downregulated, following a drastic decrease in MAPK pathway activity levels. Notably, a remarkable increase in phosphorylation levels of p38 and JAK/STAT3 was observed in differentiated hiPSCs, while the PI3K/AKT and JNK pathways remained active during differentiation. Our data further indicate that among the RAS paralogs, NRAS predominantly activates the MAPK pathway in hiPSCs.
conclusionCollectively, the MAPK pathway appears to be the prime signaling pathway downstream of bFGF for maintaining pluripotency in hiPSCs and among the MAPK pathways, the activity of NRAS-RAF-MEK-ERK is decreased during differentiation, whereas p38 is activated and JNK remains constant.
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