Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and H₂ S production.

ABSTRACT: Chemical compounds have recently been introduced as alternative and non-integrating inducers of pluripotent stem cell fate. However, chemical reprogramming is hampered by low efficiency and the molecular mechanisms remain poorly characterized. Here, we show that inhibition of spleen tyrosine kinase (Syk) by R406 significantly promotes mouse chemical reprogramming. Mechanistically, R406 alleviates Syk / calcineurin (Cn) / nuclear factor of activated T cells (NFAT) signaling-mediated suppression of glycine, serine, and threonine metabolic genes and dependent metabolites. Syk inhibition upregulates glycine level and downstream transsulfuration cysteine biosynthesis, promoting cysteine metabolism and cellular hydrogen sulfide (H₂ S) production. This metabolic rewiring decreased oxid

SUBMITTER: Wang W 

PROVIDER: S-EPMC8167362 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature