Germ Cell Development and Epigenetics
Research Group Head
Germ cells are specialised cells found in the developing testes and ovaries that form sperm in males, or oocytes (eggs) in females. Sperm and oocytes transmit the parent’s genetic and epigenetic information to the offspring.
Epigenetic modifications to the chromatin (DNA plus the proteins that package it) provide a long-term “directory” or “memory” of which genes should be switched on or off in each cell, and thereby underpin cell identity and organ function. Conversely, disrupted epigenetic states occur in diseases including cancer, metabolic and behavioural disorders.
Importantly, epigenetic modifications are reversible in normal cells, allowing gene activity to be changed when necessary. This occurs most extensively in developing germ cells in which epigenetic information is re-set to equip the sperm and oocyte with the appropriate epigenetic information for directing embryonic and post-natal development in the offspring.
However, epigenetic programming is susceptible to alteration by environmental influences such as chemicals, diet and drugs. Significantly, altered epigenetic states can also be transmitted to the next generation and may affect health and development in the offspring. Such changes may contribute to the developmental origins of health and disease in a parent’s offspring.
The Germ Cell Development and Epigenetics group aims to improve understanding of epigenetics in the germ cells and the effects of epigenetic change on the offspring. Specifically, we use gene mutations and drugs to disrupt epigenetic modifier function in mouse germ cells to determine:
(i) the function of specific epigenetic modifiers in germ cell development, and
(ii) the ability of germ cells with altered epigenetic states to direct development in the parent’s offspring.
We also employ ex-vivo gonad culture and in-vivo mouse genetic models to examine the function of signalling pathways on epigenetics and gonad and germ cell development, providing insights into ovarian and testis cancers, and male and female infertility.
By exploring the establishment and function of epigenetic information in the germ line, our research will contribute to understanding human disease, including the impacts of novel drugs that target epigenetic processes.
Stringer JM, Western PS (2019) A step toward making human oocytes. Nat Biotechnol 37(1):24-25.
Jarred EG, Bildsoe H, Western PS (2018) Out of sight, out of mind? Germ cells and the potential impacts of epigenomic drugs. F1000Res Dec 21;7.pii:F1000 Faculty Rev-1967.
Prokopuk L, Stringer JM, White CR, Vossen RHAM, White SJ, Cohen ASA, Gibson WT, Western PS (2018) Loss of maternal EED results in postnatal overgrowth. Clin. Epigenetics. July 13;10(1):95.
Prokopuk L, Hogg K, Western, PS (2018) Pharmacological inhibtion of EZH2 disrupts the female germline epigenome. Clin. Epigenetics. Mar 5;10:33.
Western PS (2018) Epigenomic drugs and the germline: Collateral damage in the home of heritability? Mol Cell Endocrinol Feb 19 pii: S0303-7207(18)30068-6.
Prokopuk L, Stringer JM, Hogg K, Elgass KD, Western PS (2017) PRC2 is required for extensive reorganisation of H3K27me3 during epigenetic reprogramming in mouse fetal germ cells. Epigenetics & Chromatin 10(1):7.
Gustin SE, Stringer JM, Hogg K, Sinclair AH and Western PS (2016) FGF9, Activin and TGFb promote testicular characteristics in an XX gonad organ culture model. Reproduction 152(5):529-543.
Gustin SE, Hogg K, Stringer JM, Rastetter RH, Pelosi E, Miles DC, Sinclair AH, Wilhelm D, Western PS (2016) WNT/β-catenin and p27/FOXL2 differentially regulate supporting cell proliferation in the developing ovary. Developmental Biology 412(2):250-260.
Hogg K, Western PS (2015) Refurbishing the germline epigenome: Out with the old, in with the new. Seminars in Cell and Developmental Biology 45:104-11.
Stringer J, Barrand S, Western PS (2013) Fine-tuning evolution: germ-line epigenetics and inheritance. Reproduction 146(1):R37-48. doi: 10.1530/REP-12-0526.