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

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


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.


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

List of Abbreviations


Cyclin dependent kinase


DNA methyltransferases


Embryonal carcinoma


Extracellular signal-related kinase


Embryonic stem cells


2-amino-3-oxobutyrate coenzyme A ligase


Glycine cleavage system


Glycine decarboxylase


Glycogen synthase kinase 3


Histone acetyltransferase




Histone methyltransferase


Inner cell mass


Induced pluripotent stem cell


Janus-associated kinases


Leukemia inhibitory factor


Leukemia inhibitory factor receptor


Mouse embryonic stem cells




Phosphorylated retinoblastoma protein


Retinoblastoma protein


S-adenosyl homocysteine




Tricarboxylic acid


Threonine dehydrogenase


Trithorax group


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© Springer Nature Switzerland AG 2019

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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