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Energy metabolism in human pluripotent stem cells and their differentiated counterparts

Varum, S and Rodrigues, AS and Moura, MB and Momcilovic, O and Easley IV, CA and Ramalho-Santos, J and van Houten, B and Schatten, G (2011) Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS ONE, 6 (6).

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Abstract

Background: Human pluripotent stem cells have the ability to generate all cell types present in the adult organism, therefore harboring great potential for the in vitro study of differentiation and for the development of cell-based therapies. Nonetheless their use may prove challenging as incomplete differentiation of these cells might lead to tumoregenicity. Interestingly, many cancer types have been reported to display metabolic modifications with features that might be similar to stem cells. Understanding the metabolic properties of human pluripotent stem cells when compared to their differentiated counterparts can thus be of crucial importance. Furthermore recent data has stressed distinct features of different human pluripotent cells lines, namely when comparing embryo-derived human embryonic stem cells (hESCs) and induced pluripotent stem cells (IPSCs) reprogrammed from somatic cells. Methodology/Principal Findings: We compared the energy metabolism of hESCs, IPSCs, and their somatic counterparts. Focusing on mitochondria, we tracked organelle localization and morphology. Furthermore we performed gene expression analysis of several pathways related to the glucose metabolism, including glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle. In addition we determined oxygen consumption rates (OCR) using a metabolic extracellular flux analyzer, as well as total intracellular ATP levels by high performance liquid chromatography (HPLC). Finally we explored the expression of key proteins involved in the regulation of glucose metabolism. Conclusions/Findings: Our results demonstrate that, although the metabolic signature of IPSCs is not identical to that of hESCs, nonetheless they cluster with hESCs rather than with their somatic counterparts. ATP levels, lactate production and OCR revealed that human pluripotent cells rely mostly on glycolysis to meet their energy demands. Furthermore, our work points to some of the strategies which human pluripotent stem cells may use to maintain high glycolytic rates, such as high levels of hexokinase II and inactive pyruvate dehydrogenase (PDH). © 2011 Varum et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Varum, S
Rodrigues, AS
Moura, MB
Momcilovic, O
Easley IV, CA
Ramalho-Santos, J
van Houten, Bbev15@pitt.eduBEV15
Schatten, Ggps15@pitt.eduGPS15
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLudgate, MarianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 22 June 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0020914
Schools and Programs: School of Medicine > Pharmacology and Chemical Biology
Refereed: Yes
MeSH Headings: Blotting, Western; Cell Differentiation; Cell Line; Chromatography, High Pressure Liquid; Energy Metabolism; Gene Expression Profiling; Humans; Immunohistochemistry; Mitochondria--metabolism; Oxidative Phosphorylation; Oxygen Consumption; Pluripotent Stem Cells--cytology; Pluripotent Stem Cells--metabolism; Reverse Transcriptase Polymerase Chain Reaction; Transduction, Genetic
Other ID: NLM PMC3117868
PubMed Central ID: PMC3117868
PubMed ID: 21698063
Date Deposited: 05 Sep 2012 17:35
Last Modified: 04 Feb 2019 15:58
URI: http://d-scholarship.pitt.edu/id/eprint/13870

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