Glutamine/glutamate metabolism rewiring in reprogrammed human hepatocyte-like cells.

ABSTRACT: Human dermal fibroblasts can be reprogrammed into hepatocyte-like (HEP-L) cells by the expression of a set of transcription factors. Yet, the metabolic rewiring suffered by reprogrammed fibroblasts remains largely unknown. Here we report, using stable isotope-resolved metabolic analysis in combination with metabolomic-lipidomic approaches that HEP-L cells mirrors glutamine/glutamate metabolism in primary cultured human hepatocytes that is very different from parental human fibroblasts. HEP-L cells diverge glutamine from multiple metabolic pathways into deamidation and glutamate secretion, just like periportal hepatocytes do. Exceptionally, glutamine contribution to lipogenic acetyl-CoA through reductive carboxylation is increased in HEP-L cells, recapitulating that of primary cultured huma

SUBMITTER: Ballester M 

PROVIDER: S-EPMC6884617 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature