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Threonine Catabolism: An Unexpected Epigenetic Regulator of Mouse Embryonic Stem Cells

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Handbook of Nutrition, Diet, and Epigenetics

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Abstract

Mouse embryonic stem cells (mESCs) are prototypical in vitro models of pluripotent stem cells. They are characterized by a capacity for infinite self-renewal while retaining the ability to differentiate into each of the cell types of the embryo. The maintenance of their pluripotent state relies on a complex regulatory network involving cytokine signaling and transcriptional controls at genetic and epigenetic levels. More recently, it has become evident that mESC pluripotency requires a specific nutritional environment. We now understand that mESC pluripotency is critically dependent on threonine catabolism for provision of one- and two-carbon donors for pluripotency-related chromatin modifications. In this chapter, we provide a comprehensive overview of the cellular processes required for the maintenance of mESC pluripotency, including signaling pathways, transcriptional networks, and epigenetic regulation. In addition, we discuss the latest developments concerning the unique dependence of mESC on threonine and the role of the amino acid in establishing the epigenetic status required for mESC self-renewal.

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Abbreviations

CDK:

Cyclin dependent kinase

DNMT:

DNA methyltransferases

EC:

Embryonal carcinoma

Erk:

Extracellular signal-related kinase

ESC:

Embryonic stem cells

GCAT:

2-amino-3-oxobutyrate coenzyme A ligase

GCS:

Glycine cleavage system

GLDC:

Glycine decarboxylase

GSK3:

Glycogen synthase kinase 3

HAT:

Histone acetyltransferase

hCys:

Homocysteine

HMT:

Histone methyltransferase

ICM:

Inner cell mass

iPSC:

Induced pluripotent stem cell

JAK:

Janus-associated kinases

LIF:

Leukemia inhibitory factor

LIFR:

Leukemia inhibitory factor receptor

mESC:

Mouse embryonic stem cells

Met:

Methionine

pRB:

Phosphorylated retinoblastoma protein

RB:

Retinoblastoma protein

SAH:

S-adenosyl homocysteine

SAM:

S-adenosylmethionine

TCA:

Tricarboxylic acid

TDH:

Threonine dehydrogenase

TrxG:

Trithorax group

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Authors and Affiliations

  1. Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA

    Ruta Jog, Guohua Chen, Todd Leff & Jian Wang

  2. Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, USA

    Jian Wang

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  1. Ruta Jog
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  2. Guohua Chen
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  3. Todd Leff
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  4. Jian Wang
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Correspondence to Jian Wang .

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Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

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Jog, R., Chen, G., Leff, T., Wang, J. (2019). Threonine Catabolism: An Unexpected Epigenetic Regulator of Mouse Embryonic Stem Cells. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-55530-0_103

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  • DOI: https://doi.org/10.1007/978-3-319-55530-0_103

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