Home > Publications database > Establishment of neuronal and glial competence of neural stem cells requires distinct enzymatic activities of TET enzymes. > print |
001 | 303362 | ||
005 | 20250810021938.0 | ||
024 | 7 | _ | |a 10.1016/j.stemcr.2025.102595 |2 doi |
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037 | _ | _ | |a DKFZ-2025-01612 |
041 | _ | _ | |a English |
082 | _ | _ | |a 610 |
100 | 1 | _ | |a Ebert, Blake C |b 0 |
245 | _ | _ | |a Establishment of neuronal and glial competence of neural stem cells requires distinct enzymatic activities of TET enzymes. |
260 | _ | _ | |a Maryland Heights, MO |c 2025 |b Cell Press |
336 | 7 | _ | |a article |2 DRIVER |
336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1754299559_1226 |2 PUB:(DE-HGF) |
336 | 7 | _ | |a ARTICLE |2 BibTeX |
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520 | _ | _ | |a Ten-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. |
536 | _ | _ | |a 311 - Zellbiologie und Tumorbiologie (POF4-311) |0 G:(DE-HGF)POF4-311 |c POF4-311 |f POF IV |x 0 |
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650 | _ | 7 | |a 5caC |2 Other |
650 | _ | 7 | |a 5fC |2 Other |
650 | _ | 7 | |a 5hmC |2 Other |
650 | _ | 7 | |a DNA demethylation |2 Other |
650 | _ | 7 | |a Neural stem cells |2 Other |
650 | _ | 7 | |a TET enzymes |2 Other |
650 | _ | 7 | |a glial |2 Other |
650 | _ | 7 | |a neurons |2 Other |
700 | 1 | _ | |a MacArthur, Ian C |b 1 |
700 | 1 | _ | |a Ketchum, Harmony C |b 2 |
700 | 1 | _ | |a Musheev, Michael |b 3 |
700 | 1 | _ | |a Niehrs, Christof |0 P:(DE-He78)483ad6be7d7fe19e48db9cce86efd70e |b 4 |u dkfz |
700 | 1 | _ | |a Suzuki, Masako |b 5 |
700 | 1 | _ | |a Dawlaty, Meelad M |b 6 |
773 | _ | _ | |a 10.1016/j.stemcr.2025.102595 |g p. 102595 - |0 PERI:(DE-600)2720528-9 |p nn |t Stem cell reports |v nn |y 2025 |x 2213-6711 |
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