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

PLoS Comput Biol. 2020 Apr 16;16(4):e1007780. doi: 10.1371/journal.pcbi.1007780. eCollection 2020 Apr.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors
  • Cells, Cultured
  • Computational Biology
  • Extracellular Space / chemistry
  • Extracellular Space / metabolism
  • Glutamine / metabolism
  • Glutamine / pharmacology
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / drug effects
  • Induced Pluripotent Stem Cells* / metabolism
  • Metabolic Networks and Pathways / physiology*
  • Neural Stem Cells* / cytology
  • Neural Stem Cells* / drug effects
  • Neural Stem Cells* / metabolism

Substances

  • Glutamine

Grants and funding

JVS acknowledges his PhD fellowship (PD/BD/52474/2014) to Fundação para a Ciência e a Tecnologia (FCT), Portugal (https://www.fct.pt/). This work was supported by iNOVA4Health UID/Multi/04462/2013), a program co-funded by FCT/Ministério da Ciência, Tecnologia e do Ensino Superior and by FEDER under the PT2020 Partnership Agreement (http://www.inova4health.com/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.