DNMT3B deficiency alters mitochondrial biogenesis and α-ketoglutarate levels in human embryonic stem cells.
Artur Cieslar-PobudaTheresa D AhrensSafak CaglayanSidney BehringerLuciana HannibalJudith StaerkPublished in: Stem cells (Dayton, Ohio) (2020)
Embryonic stem cell renewal and differentiation is regulated by metabolites that serve as cofactors for epigenetic enzymes. An increase of α-ketoglutarate (α-KG), a cofactor for histone and DNA demethylases, triggers multilineage differentiation in human embryonic stem cells (hESCs). To gain further insight into how the metabolic fluxes in pluripotent stem cells can be influenced by inactivating mutations in epigenetic enzymes, we generated hESCs deficient for de novo DNA methyltransferases (DNMTs) 3A and 3B. Our data reveal a bidirectional dependence between DNMT3B and α-KG levels: a-KG is significantly upregulated in cells deficient for DNMT3B, while DNMT3B expression is downregulated in hESCs treated with α-KG. In addition, DNMT3B null hESCs exhibit a disturbed mitochondrial fission and fusion balance and a switch from glycolysis to oxidative phosphorylation. Taken together, our data reveal a novel link between DNMT3B and the metabolic flux of hESCs.
Keyphrases
- dna methylation
- embryonic stem cells
- genome wide
- pluripotent stem cells
- gene expression
- endothelial cells
- stem cells
- oxidative stress
- circulating tumor
- induced apoptosis
- poor prognosis
- induced pluripotent stem cells
- cell free
- big data
- ms ms
- single molecule
- long non coding rna
- mesenchymal stem cells
- machine learning
- signaling pathway
- nucleic acid
- replacement therapy