Publication Date:
2012-11-03
Description:
Threonine is the only amino acid critically required for the pluripotency of mouse embryonic stem cells (mESCs), but the detailed mechanism remains unclear. We found that threonine and S-adenosylmethionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that threonine provides a substantial fraction of both the cellular glycine and the acetyl-coenzyme A (CoA) needed for SAM synthesis. Depletion of threonine from the culture medium or threonine dehydrogenase (Tdh) from mESCs decreased accumulation of SAM and decreased trimethylation of histone H3 lysine 4 (H3K4me3), leading to slowed growth and increased differentiation. Thus, abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652341/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652341/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shyh-Chang, Ng -- Locasale, Jason W -- Lyssiotis, Costas A -- Zheng, Yuxiang -- Teo, Ren Yi -- Ratanasirintrawoot, Sutheera -- Zhang, Jin -- Onder, Tamer -- Unternaehrer, Juli J -- Zhu, Hao -- Asara, John M -- Daley, George Q -- Cantley, Lewis C -- 4R00CA168997-02/CA/NCI NIH HHS/ -- K08 CA157727/CA/NCI NIH HHS/ -- R00 CA168997/CA/NCI NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01 GM56203/GM/NIGMS NIH HHS/ -- RC2 HL102815/HL/NHLBI NIH HHS/ -- RC2HL102815/HL/NHLBI NIH HHS/ -- U01 HL100001/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jan 11;339(6116):222-6. doi: 10.1126/science.1226603. Epub 2012 Nov 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23118012" target="_blank"〉PubMed〈/a〉
Keywords:
Acetyl Coenzyme A/metabolism
;
Alcohol Oxidoreductases/metabolism
;
Animals
;
Cell Differentiation
;
Cells, Cultured
;
Cellular Reprogramming
;
Culture Media
;
Embryonic Stem Cells/*cytology/*metabolism
;
Epigenesis, Genetic
;
Fibroblasts/cytology/metabolism
;
Glycine/metabolism
;
Histones/*metabolism
;
Induced Pluripotent Stem Cells/cytology/*metabolism
;
Metabolic Networks and Pathways
;
Methylation
;
Mice
;
Pluripotent Stem Cells/cytology/*metabolism
;
S-Adenosylmethionine/*metabolism
;
Threonine/*metabolism
;
Transcription Factors/genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
