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@ARTICLE{Ebert:303362,
author = {B. C. Ebert and I. C. MacArthur and H. C. Ketchum and M.
Musheev and C. Niehrs$^*$ and M. Suzuki and M. M. Dawlaty},
title = {{E}stablishment of neuronal and glial competence of neural
stem cells requires distinct enzymatic activities of {TET}
enzymes.},
journal = {Stem cell reports},
volume = {nn},
issn = {2213-6711},
address = {Maryland Heights, MO},
publisher = {Cell Press},
reportid = {DKFZ-2025-01612},
pages = {nn},
year = {2025},
note = {DKFZ-ZMBH Alliance / epub},
abstract = {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.},
keywords = {5caC (Other) / 5fC (Other) / 5hmC (Other) / DNA
demethylation (Other) / Neural stem cells (Other) / TET
enzymes (Other) / glial (Other) / neurons (Other)},
cin = {A050},
ddc = {610},
cid = {I:(DE-He78)A050-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40749667},
doi = {10.1016/j.stemcr.2025.102595},
url = {https://inrepo02.dkfz.de/record/303362},
}