Metabolic oxidation regulates embryonic stem cell differentiation

Yanes, Óscar; Clark, Julie; Wong, Diana; Patti, Gary J.; Sánchez-Ruíz, Antonio; Benton, H. Paul; Trauger, Sunia A.; Desponts, Caroline; Ding, Sheng; Siuzdak, Gary

doi:10.1038/nchembio.364

Cited by 456 publications

(403 citation statements)

References 38 publications

Supporting

Mentioning

384

Contrasting

Order By: Relevance

“…The finding that lipid stores diminished during the loss of pluripotency by hiPSCs corroborates hESC differentiation data previously published by our laboratory and other groups [11,15]. The reasons why lipid depletion occurs during the differentiation process is unclear but one group has suggested that the eicosanoid pathway may play an important role [36]. They discovered that the inhibition of the eicosanoid signaling pathway of murine embryonic stem cells fostered pluripotency when the cells underwent neural differentiation.…”

Section: Undifferentiated Human Embryonic Stem Cells and Human Inducesupporting

confidence: 89%

Fourier transform infrared microspectroscopy reveals unique phenotypes for human embryonic and induced pluripotent stem cell lines and their progeny

Cao

McNaughton

et al. 2013

Journal of Biophotonics

View full text Add to dashboard Cite

Journal of BIOPHOTONICSFourier transform infrared (FTIR) microspectroscopy was employed to elucidate the macromolecular phenotype of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) and their differentiated progeny. Undifferentiated hESCs and hiPSC lines were found to be not clearly distinguishable from each other. However, although both hESC and hiPSC variants appeared to undergo similar changes during differentiation in terms of cell surface antigens, the derived cell types from all cell lines could be discriminated using FTIR spectroscopy. We foresee a possible future role for FTIR microspectroscopy as a powerful and objective investigative and quality control tool in regenerative medicine.Bright field image of human embryonic stem cells in culture.

show abstract

Section: Undifferentiated Human Embryonic Stem Cells and Human Inducesupporting

confidence: 89%

Fourier transform infrared microspectroscopy reveals unique phenotypes for human embryonic and induced pluripotent stem cell lines and their progeny

Cao

McNaughton

et al. 2013

Journal of Biophotonics

View full text Add to dashboard Cite

show abstract

“…Stem cells, including embryonic stem cells (ESC), hematopoietic stem cells (HSC), and induced pluripotent stem cells (iPSC), appear to rely on glycolysis rather than mitochondrial respiration for the production of ATP (reviewed in [29]). The metabolomes of iPSC and ESC are closely related to each other and are consistent with observations that inhibition of oxidative pathways sustains pluripotency [28,41]. Specifically, iPSC and ESC have a decrease in the metabolites derived from mitochondrial respiration and an increase in glycolytic intermediates [28].…”

Section: Cell Type-specific Metabolic Activitysupporting

confidence: 64%

FASNating Targets of Metformin in Breast Cancer Stem-Like Cells

Wellberg

Anderson

2014

HORM CANC

View full text Add to dashboard Cite

Diabetes, Breast Cancer, and MetforminEmerging data suggest that metformin treatment is associated with reduced breast cancer incidence and mortality for individuals with type II diabetes [7,6,17]. For years, many studies have been done to investigate the possible direct and indirect effects of metformin on cancers of various origins. In diabetic patients, metformin improves metabolic function by promoting muscle glucose uptake and lowering hepatic gluconeogenesis [14,15,36]. In cultured cancer and normal cells, metformin has pleiotropic effects, including decreasing mitochondrial electron transport complex I activity, increasing the cellular AMP to ATP ratio, and activating the AMPK signaling pathway. The consequence of this is reduced protein translation, DNA synthesis, and cell proliferation. In isolated cancer stem-like cells (CSC), metformin's targets range from inflammation [13], to micro-RNAs [1], to the synthesis of nucleotide triphosphates [16]. The diversity of responses elicited by metformin from different tissues and from the specific cell types within those tissues suggests that metformin may be a valuable therapeutic for the treatment of a variety of cancers at many stages of tumor progression. Indeed, scores of clinical trials aiming to investigate the therapeutic effects of metformin for patients with cancer are either planned or ongoing. For breast cancer, large trials are open for patients with early-stage disease (NCT01101438) and metastatic disease (NCT01310231). The results of these trials are highly anticipated and will likely answer many lingering questions about the efficacy of metformin against cancer in nondiabetic patients. Short-term trials have also been conducted to evaluate the effects of metformin on breast tumor cell proliferation (NCT00897884) and tumor cell metabolism (NCT01266486).In this issue, Wahdan-Alaswad et al. demonstrate that in ER/PR/HER2-negative (triple negative (TN)) breast cancer cells metformin treatment targets fatty acid synthase (FASN) through a miR193b-dependent mechanism. Specifically, in TN breast cancer cells, metformin upregulated miR193b, which directly targeted the FASN mRNA resulting in decreased FASN protein levels. This was associated with reduced proliferation and increased apoptosis. Gene expression profiling also revealed changes in other metabolic enzymes, including members of the cholesterol biosynthesis pathway, suggesting that metformin may impact cancer cell lipid metabolism networks at multiple nodes. One limitation of this study is that the levels of cellular fatty acids were not quantified. Presumably, the amounts of de novo synthesized fatty acids correlate with the levels of FASN protein. In cancer cells, FASN expression is regulated by the HER2/Neu and PI3K signaling pathways, steroid hormones, and genomic amplification [20,34,37,42]; however, the spectrum of fatty acid products and the kinetics of the FASN reaction can be altered by effector proteins [21,32]. Interestingly, the effects of metformin on miR193b and FASN were only observe...

show abstract

“…GSH is a critical regulator of redox balance and is required for normal embryo development (Ufer et al, 2010;Yanes et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Glyceryl trinitrate metabolism in the quail embryo by the glutathione S-transferases leads to a perturbation in redox status and embryotoxicity

Bardai

Hales

Sunahara

2013

Comparative Biochemistry and Physiology Part B: Biochemistry an

View full text Add to dashboard Cite

/npsi/ctrl?lang=en http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/ctrl?lang=fr Access and use of this website and the material on it are subject to the Terms and Conditions set forth at http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/jsp/nparc_cp.jsp?lang=en NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. For the publisher's version, please access the DOI link below./ Pour consulter la version de l'éditeur, utilisez le lien DOI ci-dessous.http://dx.doi.org/10. 1016/j.cbpb.2013.04.001 Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 165, 3, pp. 153-164, 2013-04-12 Glyceryl trinitrate metabolism in the quail embryo by the glutathione Stransferases leads to a perturbation in redox status and embryotoxicity Bardai, Ghalib K.; Hales, Barbara F.; Sunahara, Geoffrey I. induces malformations that were associated in previous studies with an increase in protein nitration.Increased nitration suggests metabolism of GTN by the embryo. The goals of this study were to characterize the enzymes and co-factors required for GTN metabolism by quail embryos, and to determine the effects of in ovo treatment with N-acetyl cysteine (NAC), a precursor of glutathione (GSH), on GTN embryotoxicity. GTN treatment of quail embryo resulted in an increase in nitrite, a 2 decrease in total GSH, and an increase in the ratio of NADP+/NADPH, indicating that redox balance may be compromised in exposed embryos. Glutathione S-transferases (GSTs; EC 2.5.1.18) purified from the whole embryo (K m 0.84 mM; V max 36 µM/min) and the embryonic eye (K m 0.20 mM; V max 30 µM/min) had GTN-metabolizing activity (1436 and 34 nmol/min/mg, respectively); the addition of ethacrynic acid, an inhibitor of GST activity, decreased GTN metabolism. Peptide sequencing of the GST isozymes indicated that alpha-or mu-type GSTs in the embryo and embryonic eye had GTN metabolizing activity. NAC co-treatment partially protected against the effects of GTN exposure. Thus, GTN denitration by quail embryo GSTs may represent a key initial step in the developmental toxicity of GTN.

show abstract

Metabolic oxidation regulates embryonic stem cell differentiation

Cited by 456 publications

References 38 publications

Fourier transform infrared microspectroscopy reveals unique phenotypes for human embryonic and induced pluripotent stem cell lines and their progeny

Fourier transform infrared microspectroscopy reveals unique phenotypes for human embryonic and induced pluripotent stem cell lines and their progeny

FASNating Targets of Metformin in Breast Cancer Stem-Like Cells

Glyceryl trinitrate metabolism in the quail embryo by the glutathione S-transferases leads to a perturbation in redox status and embryotoxicity

Contact Info

Product

Resources

About