Stem cell fate is largely determined by cellular signaling networks and is heavily dependent on the supplementation of exogenous recombinant proteins into culture media; however, uneven distribution and inconsistent stability of recombinant proteins are closely associated with the spontaneous differentiation of pluripotent stem cells (PSCs) and result in significant costs in large-scale manufacturing. Here, we report a novel PSC culture system via wirelessly controllable optical activation of the fibroblast growth factor (FGF) signaling pathway without the need for supplementation of recombinant FGF2 protein, a key molecule for maintaining pluripotency of PSCs. Using a fusion protein between the cytoplasmic region of the FGF receptor-1 and a light-oxygen-voltage domain, we achieved tunable, blue light-dependent activation of FGF signaling in human and porcine PSCs. Our data demonstrate that a highly controllable optical stimulation of the FGF signaling pathway is sufficient for long-term maintenance of PSCs, without the loss of differentiation potential into three germ layers. This culture system will be a cost-effective platform for a large-scale stem cell culture.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120222 | DOI Listing |
Dev Biol
January 2025
Biology Department, Texas A&M University, College Station, TX 7843-3258. Electronic address:
During development of the vertebrate inner ear, sensory epithelia and neurons of the statoacoustic ganglion (SAG) arise from lineage-restricted progenitors that proliferate extensively before differentiating into mature post-mitotic cell types. Development of progenitors is regulated by Fgf, Wnt and Notch signaling, but how these pathways are coordinated to achieve an optimal balance of proliferation and differentiation is not well understood. Here we investigate the role in zebrafish of Foxm1, a transcription factor commonly associated with proliferation in developing tissues and tumors.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czechia.
Impaired fibroblast growth factor receptor (FGFR) signaling is associated with many human conditions, including growth disorders, degenerative diseases, and cancer. Current FGFR therapeutics are based on chemical inhibitors of FGFR tyrosine kinase activity (TKIs). However, FGFR TKIs are limited in their target specificity as they generally inhibit all FGFRs and other receptor tyrosine kinases.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, United States.
Sci Rep
January 2025
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
α-Klotho (KLA) is a type-1 membranous protein that can associate with fibroblast growth factor receptor (FGFR) to form co-receptor for FGF23. The ectodomain of unassociated KLA is shed as soluble KLA (sKLA) to exert FGFR/FGF23-independent pleiotropic functions. The previously determined X-ray crystal structure of the extracellular region of sKLA in complex with FGF23 and FGFR1c suggests that sKLA functions solely as an on-demand coreceptor for FGF23.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Isoniazid and rifampicin co-therapy are the main causes of anti-tuberculosis drug-induced liver injury (ATB-DILI) and acute liver failure, seriously threatening human health. However, its pathophysiology is not fully elucidated. Growing evidences have shown that fibroblast growth factors (FGFs) play a critical role in diverse aspects of liver pathophysiology.
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