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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2020.120222DOI Listing

Publication Analysis

Top Keywords

fgf signaling
16
culture system
12
controllable optical
12
signaling pathway
12
system wirelessly
8
wirelessly controllable
8
optical stimulation
8
stimulation fgf
8
stem cell
8
recombinant proteins
8

Similar Publications

Foxm1 promotes differentiation of neural progenitors in the zebrafish inner ear.

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 PDF

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 PDF

Understanding Folding of bFGF and Potential Cellular Protective Mechanisms of Neural Cells.

Biochemistry

January 2025

Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, United States.

Article Synopsis
  • Traumatic brain injury (TBI) affects many individuals, especially veterans and athletes, and has serious, long-term consequences for brain health.
  • Current research explores the role of fibroblast growth factor (FGF) proteins in protecting cells, highlighting knowledge gaps regarding how heparin and similar molecules activate bFGF and how mutations affect its stability.
  • Using temperature replica exchange, the study identified a new binding site on bFGF and revealed that various sugars affect bFGF interactions similarly to heparin, underscoring the need for a deeper understanding of TBI mechanisms for better treatment development.
View Article and Find Full Text PDF

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 PDF

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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!