Metabolic Determinants of Embryonic Development and Stem Cell Fate

Overview

Journal Reprod Fertil Dev

Specialty Reproductive Medicine

Date 2014 Dec 5

PMID 25472047

Citations 35

Authors

Clifford D L Folmes

Andre Terzic

Affiliations

Soon will be listed here.

Abstract

Decoding stem cell metabolism has implicated a tight linkage between energy metabolism and cell fate regulation, a dynamic interplay vital in the execution of developmental and differentiation programs. The inherent plasticity in energy metabolism enables prioritisation of metabolic pathways in support of stage-specific demands. Beyond traditional support of energetic needs, intermediate metabolism may also dictate cell fate choices through regulation of cellular signalling and epigenetic regulation of gene expression. The notion of a 'metabolism-centric' control of stem cell differentiation has been informed by developmental embryogenesis based upon an on-demand paradigm paramount in defining diverse developmental behaviours, from a post-fertilisation nascent zygote to complex organogenesis leading to adequate tissue formation and maturation. Monitored through natural or bioengineered stem cell surrogates, nutrient-responsive metabolites are identified as mediators of cross-talk between metabolic flux, cell signalling and epigenetic regulation charting, collectively, whether a cell will self-renew to maintain progenitor pools, lineage specify to ensure tissue (re)generation or remain quiescent to curb stress damage. Thus, bioenergetics are increasingly recognised as integral in governing stemness and associated organogenic decisions, paving the way for metabolism-defined targets in control of embryology, stem cell biology and tissue regeneration.

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References

Bracha A, Ramanathan A, Huang S, Ingber D, Schreiber S . Carbon metabolism-mediated myogenic differentiation. Nat Chem Biol. 2010; 6(3):202-204. PMC: 2822028. DOI: 10.1038/nchembio.301. View

Chung S, Arrell D, Faustino R, Terzic A, Dzeja P . Glycolytic network restructuring integral to the energetics of embryonic stem cell cardiac differentiation. J Mol Cell Cardiol. 2010; 48(4):725-34. PMC: 2837789. DOI: 10.1016/j.yjmcc.2009.12.014. View

Folmes C, Terzic A . Stem cell lineage specification: you become what you eat. Cell Metab. 2014; 20(3):389-91. PMC: 4155325. DOI: 10.1016/j.cmet.2014.08.006. View

Zheng P, Vassena R, Latham K . Effects of in vitro oocyte maturation and embryo culture on the expression of glucose transporters, glucose metabolism and insulin signaling genes in rhesus monkey oocytes and preimplantation embryos. Mol Hum Reprod. 2007; 13(6):361-71. DOI: 10.1093/molehr/gam014. View

Mandal S, Lindgren A, Srivastava A, Clark A, Banerjee U . Mitochondrial function controls proliferation and early differentiation potential of embryonic stem cells. Stem Cells. 2011; 29(3):486-95. PMC: 4374603. DOI: 10.1002/stem.590. View

Facucho-Oliveira J, Alderson J, Spikings E, Egginton S, St John J . Mitochondrial DNA replication during differentiation of murine embryonic stem cells. J Cell Sci. 2007; 120(Pt 22):4025-34. DOI: 10.1242/jcs.016972. View

Folmes C, Nelson T, Martinez-Fernandez A, Arrell D, Lindor J, Dzeja P . Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 2011; 14(2):264-71. PMC: 3156138. DOI: 10.1016/j.cmet.2011.06.011. View

Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S . Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell. 2009; 5(3):237-41. DOI: 10.1016/j.stem.2009.08.001. View

Hansson J, Rafiee M, Reiland S, Polo J, Gehring J, Okawa S . Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency. Cell Rep. 2012; 2(6):1579-92. PMC: 4438680. DOI: 10.1016/j.celrep.2012.10.014. View

10.

Folmes C, Dzeja P, Nelson T, Terzic A . Metabolic plasticity in stem cell homeostasis and differentiation. Cell Stem Cell. 2012; 11(5):596-606. PMC: 3593051. DOI: 10.1016/j.stem.2012.10.002. View

11.

Motta P, Nottola S, Makabe S, Heyn R . Mitochondrial morphology in human fetal and adult female germ cells. Hum Reprod. 2000; 15 Suppl 2:129-47. DOI: 10.1093/humrep/15.suppl_2.129. View

12.

Piccoli C, Ria R, Scrima R, Cela O, DAprile A, Boffoli D . Characterization of mitochondrial and extra-mitochondrial oxygen consuming reactions in human hematopoietic stem cells. Novel evidence of the occurrence of NAD(P)H oxidase activity. J Biol Chem. 2005; 280(28):26467-76. DOI: 10.1074/jbc.M500047200. View

13.

Chung S, Dzeja P, Faustino R, Perez-Terzic C, Behfar A, Terzic A . Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells. Nat Clin Pract Cardiovasc Med. 2007; 4 Suppl 1:S60-7. PMC: 3232050. DOI: 10.1038/ncpcardio0766. View

14.

Folmes C, Dzeja P, Nelson T, Terzic A . Mitochondria in control of cell fate. Circ Res. 2012; 110(4):526-9. PMC: 3491643. DOI: 10.1161/RES.0b013e31824ae5c1. View

15.

PIKO L, Taylor K . Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos. Dev Biol. 1987; 123(2):364-74. DOI: 10.1016/0012-1606(87)90395-2. View

16.

Lonergan T, Bavister B, Brenner C . Mitochondria in stem cells. Mitochondrion. 2007; 7(5):289-96. PMC: 3089799. DOI: 10.1016/j.mito.2007.05.002. View

17.

PIKO L, Matsumoto L . Number of mitochondria and some properties of mitochondrial DNA in the mouse egg. Dev Biol. 1976; 49(1):1-10. DOI: 10.1016/0012-1606(76)90253-0. View

18.

Knobloch M, Braun S, Zurkirchen L, von Schoultz C, Zamboni N, Arauzo-Bravo M . Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature. 2012; 493(7431):226-30. PMC: 3587167. DOI: 10.1038/nature11689. View

19.

Tormos K, Anso E, Hamanaka R, Eisenbart J, Joseph J, Kalyanaraman B . Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab. 2011; 14(4):537-44. PMC: 3190168. DOI: 10.1016/j.cmet.2011.08.007. View

20.

Zhu S, Li W, Zhou H, Wei W, Ambasudhan R, Lin T . Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell. 2010; 7(6):651-5. PMC: 3812930. DOI: 10.1016/j.stem.2010.11.015. View