2026-08-29T14:07:45Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/258542025-12-18T12:57:06Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Mulet, Isabel author Grueso-Cortina, Carmen author Cortés-Cano, Mireia author Gerovska, Daniela author Wu, Guangming author Iakab, Stefania Alexandra author Jimenez-Blasco, Daniel author Curtabbi, Andrea author Hernansanz-Agustín, Pablo author Ketchum, Harmony author Manjarrés-Raza, Israel author Wunderlich, F Thomas author Bolaños, Juan Pedro author Dawlaty, Meelad M author Hopf, Carsten author Enríquez, José Antonio author Araúzo-Bravo, Marcos J author Tapia, Natalia author 2024-11-18 TET-family members play a critical role in cell fate commitment. Indeed, TET3 is essential to postnatal development due to yet unknown reasons. To define TET3 function in cell differentiation, we have profiled the intestinal epithelium at single-cell level from wild-type and Tet3 knockout mice. We have found that Tet3 is mostly expressed in differentiated enterocytes. In the absence of TET3, enterocytes exhibit an aberrant differentiation trajectory and do not acquire a physiological cell identity due to an impairment in oxidative phosphorylation, specifically due to an ATP synthase assembly deficiency. Moreover, spatial metabolomics analysis has revealed that Tet3 knockout enterocytes exhibit an unphysiological metabolic profile when compared with their wild-type counterparts. In contrast, no metabolic differences have been observed between both genotypes in the stem cell compartment where Tet3 is mainly not expressed. Collectively, our findings suggest a mechanism by which TET3 regulates mitochondrial function and, thus, terminal cell differentiation at the metabolic level. Nat Commun. 2024 Nov 18;15(1):9749. Nature Communications 39557858 https://hdl.handle.net/20.500.12105/25854 TET3 regulates terminal cell differentiation at the metabolic level.