TET knockout cells transit between pluripotent states and exhibit precocious germline entry.

ABSTRACT: TET1, TET2 and TET3 are DNA demethylases with important roles in development and differentiation. To assess the contributions of TET proteins to cell function during early development, single and compound knockouts of Tet genes in mouse pluripotent embryonic stem cells (ESCs) were generated. Here, we show that TET proteins are not required to transit between naïve, formative and primed pluripotency states. Moreover, ESCs with double knockouts of Tet1 and Tet2 or triple knockouts of Tet1, Tet2 and Tet3 are phenotypically indistinguishable. TET1,2,3-deficient ESCs exhibit differentiation defects and fail to activate somatic gene expression, retaining expression of pluripotency transcription factors. Therefore, TET1 and TET2, but not TET3 act redundantly to facilitate somatic differentiation.

SUBMITTER: Pantier R 

PROVIDER: S-EPMC12669618 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature