The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming

Athanasia D. Panopoulos; Oscar Yanes; Sergio Ruiz; Yasuyuki S. Kida; Dinh Diep; Ralf Tautenhahn; Aída Herrerías; Erika M. Batchelder; Nongluk Plongthongkum; Margaret Lutz; W. Travis Berggren; Kun Zhang; Ronald M. Evans; Gary Siuzdak; Juan Carlos Izpisua Belmonte

doi:10.1038/cr.2011.177

The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming

Athanasia D. Panopoulos, Oscar Yanes, Sergio Ruiz, Yasuyuki S. Kida, Dinh Diep, Ralf Tautenhahn, Aída Herrerías, Erika M. Batchelder, Nongluk Plongthongkum, Margaret Lutz, W. Travis Berggren, Kun Zhang, Ronald M. Evans, Gary Siuzdak^*, Juan Carlos Izpisua Belmonte

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

419 Scopus citations

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.

Original language	English (US)
Pages (from-to)	168-177
Number of pages	10
Journal	Cell research
Volume	22
Issue number	1
DOIs	https://doi.org/10.1038/cr.2011.177
State	Published - Jan 2012
Externally published	Yes

Keywords

IPS cells
Metabolism
Metabolome
Reprogramming
Stem cells

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1038/cr.2011.177

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Panopoulos, A. D., Yanes, O., Ruiz, S., Kida, Y. S., Diep, D., Tautenhahn, R., Herrerías, A., Batchelder, E. M., Plongthongkum, N., Lutz, M., Berggren, W. T., Zhang, K., Evans, R. M., Siuzdak, G., & Belmonte, J. C. I. (2012). The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell research, 22(1), 168-177. https://doi.org/10.1038/cr.2011.177

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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.",

keywords = "IPS cells, Metabolism, Metabolome, Reprogramming, Stem cells",

author = "Panopoulos, {Athanasia D.} and Oscar Yanes and Sergio Ruiz and Kida, {Yasuyuki S.} and Dinh Diep and Ralf Tautenhahn and A{\'i}da Herrer{\'i}as and Batchelder, {Erika M.} and Nongluk Plongthongkum and Margaret Lutz and Berggren, {W. Travis} and Kun Zhang and Evans, {Ronald M.} and Gary Siuzdak and Belmonte, {Juan Carlos Izpisua}",

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Panopoulos, AD, Yanes, O, Ruiz, S, Kida, YS, Diep, D, Tautenhahn, R, Herrerías, A, Batchelder, EM, Plongthongkum, N, Lutz, M, Berggren, WT, Zhang, K, Evans, RM, Siuzdak, G & Belmonte, JCI 2012, 'The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming', Cell research, vol. 22, no. 1, pp. 168-177. https://doi.org/10.1038/cr.2011.177

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AU - Yanes, Oscar

AU - Ruiz, Sergio

AU - Kida, Yasuyuki S.

AU - Diep, Dinh

AU - Tautenhahn, Ralf

AU - Herrerías, Aída

AU - Batchelder, Erika M.

AU - Plongthongkum, Nongluk

AU - Lutz, Margaret

AU - Berggren, W. Travis

AU - Zhang, Kun

AU - Evans, Ronald M.

AU - Siuzdak, Gary

AU - Belmonte, Juan Carlos Izpisua

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N2 - 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.

AB - 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.

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The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming

Abstract

Keywords

ASJC Scopus subject areas

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