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.
Highlights
Over the last decade, the paradigm of metabolism being the engine for metabolic constituents has been dramatically shifted
Identification of the most tightly regulated metabolites in cellular systems has been hampered by limitations of current methodologies, which typically focus on steady-state data, overlooking transient dynamics and potential regulators
We proposed an innovative approach to face this challenge, by exploring the dynamic response of metabolic pools of human stem cells to a sudden metabolic perturbation
Summary
The paradigm of metabolism being the engine for metabolic constituents has been dramatically shifted. Metabolism generates regulatory responses [1] that affect all other molecular levels, from epigenome to proteome, through diverse action mechanisms (e.g. DNA methylation, histone acetylation) [2,3,4]. Those regulatory responses modulate key cell decisions such as proliferation, differentiation and death [5]. Inspecting the activity of metabolic pathways is an appealing approach for cell characterization. This approach can pose significant limitations, as recent literature has shown that cells fine-tune their intracellular fluxes according to momentaneous needs [6] but can change their sources of carbon and nitrogen [7]. It was found that asparagine uptake in mammalian cells preferentially occurs in a glutamine-deficient environment and does not occur when glutamine is present [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
