Gavin Kelsey

Research Summary

As well as genetic information, the egg and sperm also contribute epigenetic annotations that may influence gene activity after fertilisation. These annotations may be direct modifications of the DNA bases or of the proteins around which the DNA is wrapped into chromatin. Our goal is to understand whether, through epigenetics, factors such as a mother’s age or diet have consequences on the health of a child.
 
We examine how epigenetic states are set up in oocytes – or egg cells – and influence gene expression in the embryo. For example, repressive chromatin marks in oocytes lead to long-term silencing of genes inherited from the mother, particularly in cells that will form the placenta. We are also interested in how variations in DNA methylation come about in oocytes and whether we can use this variation as a marker for oocyte quality and embryo potential. To investigate these questions, we develop methods to profile epigenetic information in very small numbers of cells or even in single cells.

Latest Publications

LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with inflammation and endometrial function.
Jhamat N, Niazi A, Guo Y, Chanrot M, Ivanova E, Kelsey G, Bongcam-Rudloff E, Andersson G, Humblot P

Lipopolysaccharide (LPS) endotoxin stimulates pro-inflammatory pathways and is a key player in the pathological mechanisms involved in the development of endometritis. This study aimed to investigate LPS-induced DNA methylation changes in bovine endometrial epithelial cells (bEECs), which may affect endometrial function. Following in vitro culture, bEECs from three cows were either untreated (0) or exposed to 2 and 8 μg/mL LPS for 24 h.

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BMC genomics, 21, 1, 03 Jun 2020

DOI: 10.1186/s12864-020-06777-7

PMID: 32493210

A distinctive epigenetic ageing profile in human granulosa cells.
Olsen KW, Castillo-Fernandez J, Zedeler A, Freiesleben NC, Bungum M, Chan AC, Cardona A, Perry JRB, Skouby SO, Borup R, Hoffmann ER, Kelsey G, Grøndahl ML

Does women's age affect the DNA methylation (DNAm) profile differently in mural granulosa cells (MGCs) from other somatic cells?

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Human reproduction (Oxford, England), 1, 1, 31 May 2020

DOI: 10.1093/humrep/deaa071

PMID: 32474592

DNA methylation changes during preimplantation development reveal inter-species differences and reprogramming events at imprinted genes.
Ivanova E, Canovas S, Garcia-Martínez S, Romar R, Lopes JS, Rizos D, Sanchez-Calabuig MJ, Krueger F, Andrews S, Perez-Sanz F, Kelsey G, Coy P

Preimplantation embryos experience profound resetting of epigenetic information inherited from the gametes. Genome-wide analysis at single-base resolution has shown similarities but also species differences between human and mouse preimplantation embryos in DNA methylation patterns and reprogramming. Here, we have extended such analysis to two key livestock species, the pig and the cow. We generated genome-wide DNA methylation and whole-transcriptome datasets from gametes to blastocysts in both species. In oocytes from both species, a distinctive bimodal methylation landscape is present, with hypermethylated domains prevalent over hypomethylated domains, similar to human, while in the mouse the proportions are reversed.An oocyte-like pattern of methylation persists in the cleavage stages, albeit with some reduction in methylation level, persisting to blastocysts in cow, while pig blastocysts have a highly hypomethylated landscape. In the pig, there was evidence of transient de novo methylation at the 8-16 cell stages of domains unmethylated in oocytes, revealing a complex dynamic of methylation reprogramming. The methylation datasets were used to identify germline differentially methylated regions (gDMRs) of known imprinted genes and for the basis of detection of novel imprinted loci. Strikingly in the pig, we detected a consistent reduction in gDMR methylation at the 8-16 cell stages, followed by recovery to the blastocyst stage, suggesting an active period of imprint stabilization in preimplantation embryos. Transcriptome analysis revealed absence of expression in oocytes of both species of ZFP57, a key factor in the mouse for gDMR methylation maintenance, but presence of the alternative imprint regulator ZNF445. In conclusion, our study reveals species differences in DNA methylation reprogramming and suggests that porcine or bovine models may be closer to human in key aspects than in the mouse model.

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Clinical epigenetics, 12, 1, 11 May 2020

DOI: 10.1186/s13148-020-00857-x

PMID: 32393379