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

  • Ruta Jog
  • Guohua Chen
  • Todd Leff
  • Jian WangEmail author
Reference work entry

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.

Keywords

Embryonic stem cell Pluripotency Transcription regulation Epigenetic regulation Histone methylation Bivalent domain Threonine metabolism Glycine metabolism One carbon metabolism Threonine dehydrogenase 

List of 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. 1.Department of PathologyWayne State University School of MedicineDetroitUSA
  2. 2.Cardiovascular Research InstituteWayne State University School of MedicineDetroitUSA

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