Unveiling dynamic metabolic signatures in human induced pluripotent and neural stem cells

João Vasconcelos e Sá, Daniel Simão, Ana P. Terrasso, Marta M. Silva, Catarina Brito, Inês A. Isidro, Paula M. Alves, Manuel J.T. Carrondo

Research output: Contribution to journalArticlepeer-review

Abstract

Metabolism plays an essential role in cell fate decisions. However, the methods used for metabolic characterization and for finding potential metabolic regulators are still based on characterizing cellular metabolic steady-state which is dependent on the extracellular environment. In this work, we hypothesized that the response dynamics of intracellular metabolic pools to extracellular stimuli is controlled in a cell type-specific manner. We applied principles of process dynamics and control to human induced pluripotent stem cells (hiPSC) and human neural stem cells (hNSC) subjected to a sudden extracellular glutamine step. The fold-changes of steady-states and the transient profiles of metabolic pools revealed that dynamic responses were reproducible and cell type-specific. Importantly, many amino acids had conserved dynamics and readjusted their steady state concentration in response to the increased glutamine influx. Overall, we propose a novel methodology for systematic metabolic characterization and identification of potential metabolic regulators.

Original languageEnglish
Article numbere1007780
JournalPLoS Computational Biology
Volume16
Issue number4
DOIs
Publication statusPublished - Apr 2020

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