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Fang, Sherry

University of British Columbia

Primordial germ cells (PGCs) undergo dynamic epigenetic changes during development, including genome-wide erasure of DNA methylation for the establishment of a clean epigenetic slate in the developing germ cells. While this epigenetic reprogramming is essential for cellular pluripotency and gamete maturation, the underlying mechanisms remain poorly understood. In this study, we explore the developmental mechanism of methylation erasure within PGCs through several models, with our main project investigating whether the reactivation of late demethylating genes in PGCs is influenced by extrinsic signals from the genital ridges or intrinsic signals within the PGCs themselves. To address this, we examined the activation of late demethylating genes utilizing the Bax KO line to bypass apoptosis and investigate extra-gonadal PGCs. Through Oct4-eGFP and Tel7KI-eGFP reporters, we visualize the presence of ectopic PGCs and analyze the reactivation of a late demethylating gene and an imprinted reporter, respectively. Our findings demonstrate that ectopic PGCs undergo epigenetic reprogramming autonomously, independent of signals from the genital ridges. Additionally, we establish two tools for future use in investigating PGC development and imprint erasure including an in vitro PGC-like cell model with cells differentiated from Tel7KI-eGFP ESCs and a red fluorescent reporter of imprint erasure, known as the Tel7KI-mCherry. Together, our study provides insights into intrinsic mechanisms driving methylation erasure in PGCs, advancing understanding of epigenetic reprogramming in germ cell development.

Text

2024-04-29

Attribution-NoDerivatives 4.0 International

http://hdl.handle.net/2429/88096

Medical Genetics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nd/4.0/