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000303362 1001_ $$aEbert, Blake C$$b0
000303362 245__ $$aEstablishment of neuronal and glial competence of neural stem cells requires distinct enzymatic activities of TET enzymes.
000303362 260__ $$aMaryland Heights, MO$$bCell Press$$c2025
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000303362 520__ $$aTen-eleven translocation (TET1/2/3) enzymes are expressed in neural stem cells (NSCs). They iteratively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). The significance of hydroxymethylation (i.e., 5hmC) versus formylation and carboxylation (i.e., active demethylation) is undefined. We generated NSCs lacking only TET formylation and carboxylation activities (Tet-TFoCa) and compared them to NSCs lacking all three TET activities (Tet-TMut). Tet-TFoCa NSCs could differentiate into neurons but not into glial cells, while Tet-TMut NSCs could not form either cell type. Mechanistically, neuronal genes retained 5hmC at their enhancers in Tet-TFoCa NSCs and were expressed normally, consistent with the ability of these cells to form neurons. In contrast, enhancers of glial genes were hypermethylated in both Tet-TFoCa and Tet-TMut NSCs underpinning downregulation of these genes and the glial block in these cells. Our findings implicate TET-driven hydroxymethylation in establishing NSC neuronal competence and formylation and carboxylation in defining NSC glial competence.
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000303362 650_7 $$2Other$$a5hmC
000303362 650_7 $$2Other$$aDNA demethylation
000303362 650_7 $$2Other$$aNeural stem cells
000303362 650_7 $$2Other$$aTET enzymes
000303362 650_7 $$2Other$$aglial
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000303362 7001_ $$aMacArthur, Ian C$$b1
000303362 7001_ $$aKetchum, Harmony C$$b2
000303362 7001_ $$aMusheev, Michael$$b3
000303362 7001_ $$0P:(DE-He78)483ad6be7d7fe19e48db9cce86efd70e$$aNiehrs, Christof$$b4$$udkfz
000303362 7001_ $$aSuzuki, Masako$$b5
000303362 7001_ $$aDawlaty, Meelad M$$b6
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