title: The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming.
abstract: Metabolism is vital to every aspect of cell function, yet the metabolome of induced pluripotent stem cells (iPSCs) remains largely unexplored. Here we report, using an untargeted metabolomics approach, that human iPSCs share a pluripotent metabolomic signature with embryonic stem cells (ESCs) that is distinct from their parental cells, and that is characterized by changes in metabolites involved in cellular respiration. Examination of cellular bioenergetics corroborated with our metabolomic analysis, and demonstrated that somatic cells convert from an oxidative state to a glycolytic state in pluripotency. Interestingly, the bioenergetics of various somatic cells correlated with their reprogramming efficiencies. We further identified metabolites that differ between iPSCs and ESCs, which revealed novel metabolic pathways that play a critical role in regulating somatic cell reprogramming. Our findings are the first to globally analyze the metabolome of iPSCs, and provide mechanistic insight into a new layer of regulation involved in inducing pluripotency, and in evaluating iPSC and ESC equivalence.
authors: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors: Athanasia D
authors: AD
authors: Panopoulos
authors: Oscar
authors: O
authors: Yanes
authors: Sergio
authors: S
authors: Ruiz
authors: Yasuyuki S
authors: YS
authors: Kida
authors: Dinh
authors: D
authors: Diep
authors: Ralf
authors: R
authors: Tautenhahn
authors: Aída
authors: A
authors: Herrerías
authors: Erika M
authors: EM
authors: Batchelder
authors: Nongluk
authors: N
authors: Plongthongkum
authors: Margaret
authors: M
authors: Lutz
authors: W Travis
authors: WT
authors: Berggren
authors: Kun
authors: K
authors: Zhang
authors: Ronald M
authors: RM
authors: Evans
authors: Gary
authors: G
authors: Siuzdak
authors: Juan Carlos
authors: JC
authors: Izpisua Belmonte
mesh_terms: D065150:Cellular Reprogramming; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006019:Glycolysis; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D055442:Metabolome; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism