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Global metabolomics of IFNy cued neurogenic NSCs seeded on hydrogel

ABSTRACT: Neural stem cells (NSCs) provide a strategy to replace damaged neurons following traumatic central nervous system injuries. A major hurdle to translation of this therapy is that direct application of NSCs to CNS injury does not support sufficient neurogenesis due to lack of proper cues. To provide prolonged spatial cues to NSCs IFN-γ was immobilized to biomimetic hydrogel substrate to supply physical and biochemical signals to instruct the encapsulated NSCs to be neurogenic. However, the immobilization of factors, including IFN-γ, versus soluble delivery of the same factor, has been incompletely characterized especially with respect to activation of signaling and metabolism in cells over longer time points. In this study, protein and metabolite changes in NSCs induced by immobilized versus soluble IFN-γ at 7 days were evaluated. Soluble IFN-γ, refreshed daily over 7 days, elicited stronger responses in NSCs compared to immobilized IFN-γ indicating that immobilization may not sustain signaling or has altered ligand/receptor interaction and integrity. However, both IFN-γ delivery types supported increased βIII tubulin expression in parallel with canonical and non-canonical receptor-signaling compared to no IFN-γ. Global metabolomics and pathway analysis revealed that soluble and immobilized IFN-γ altered metabolic pathway activities including energy, lipid and amino acid synthesis, with soluble IFN-γ having the greatest metabolic impact overall.

ORGANISM(S): Rat Rattus Norvegicus

TISSUE(S): Brain

SUBMITTER: Hannah Baumann

PROVIDER: ST001492 | MetabolomicsWorkbench | Fri Sep 11 00:00:00 BST 2020

REPOSITORIES: MetabolomicsWorkbench

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