TET1 Facilitates Specification of Early Human Lineages Including Germ Cells

Overview

Journal iScience

Publisher Cell Press

Date 2023 Jul 17

PMID 37456839

Authors

Fei-Man Hsu

Qiu Ya Wu

Emily B Fabyanic

Alex Wei

Hao Wu

Amander T Clark

Affiliations

Soon will be listed here.

Abstract

Ten Eleven Translocation 1 (TET1) is a regulator of localized DNA demethylation through the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). To examine DNA demethylation in human primordial germ cell-like cells (hPGCLCs) induced from human embryonic stem cells (hESCs), we performed bisulfite-assisted APOBEC coupled epigenetic sequencing (bACEseq) followed by integrated genomics analysis. Our data indicates that 5hmC enriches at hPGCLC-specific NANOG, SOX17 or TFAP2C binding sites on hPGCLC induction, and this is accompanied by localized DNA demethylation. Using CRISPR-Cas9, we show that deleting the catalytic domain of TET1 reduces hPGCLC competency when starting with hESC cultured on mouse embryonic fibroblasts, and this phenotype can be rescued after transitioning hESCs to defined media and a recombinant substrate. Taken together, our study demonstrates the importance of 5hmC in facilitating hPGCLC competency, and the role of hESC culture conditions in modulating this effect.

Citing Articles

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Murase Y, Yokogawa R, Yabuta Y, Nagano M, Katou Y, Mizuyama M Nature. 2024; 631(8019):170-178.

PMID: 38768632 PMC: 11222161. DOI: 10.1038/s41586-024-07526-6.

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