Rugg-Gunn Group

Rugg-Gunn Group
Rugg-Gunn Group
Peter Rugg-Gunn
Group Leader and Head of Public Engagement
Rugg-Gunn Group

Research Summary

We are interested in understanding how the epigenome is established during human development and stem cell differentiation, and how epigenetic information changes over the life course of a person.

To research these topics, we use different types of stem cell (primarily human pluripotent stem cells), stem cell-based embryo models (blastoids and gastruloids), and donated human embryos, in combination with a variety of molecular and genetic approaches to investigate their epigenomes.

This research is important because establishing our epigenomes correctly during development is vital for establishing a healthy pregnancy, and has long lasting consequences on our health. We therefore need to know more about how it happens and why it sometimes goes wrong. Our work also provides new avenues for improving the epigenetic stability of human pluripotent stem cells, and our ability to drive their specialisation towards useful cell types, which are essential requirements to fulfill their promise in regenerative medicine. 

Latest Publications

Rosspopoff O, Cazottes E, Huret C, Loda A, Collier AJ, Casanova M, Rugg-Gunn PJ, Heard E, Ouimette JF, Rougeulle C Epigenetics

X chromosome inactivation (XCI) is an essential process, yet it initiates with remarkable diversity in various mammalian species. XIST, the main trigger of XCI, is controlled in the mouse by an interplay of lncRNA genes (LRGs), some of which evolved concomitantly to XIST and have orthologues across all placental mammals. Here, we addressed the functional conservation of human orthologues of two such LRGs, FTX and JPX. By combining analysis of single-cell RNA-seq data from early human embryogenesis with various functional assays in matched human and mouse pluripotent stem- or differentiated post-XCI cells, we demonstrate major functional differences for these orthologues between species, independently of primary sequence conservation. While the function of FTX is not conserved in humans, JPX stands as a major regulator of XIST expression in both species. However, we show that different entities of JPX control the production of XIST at various steps depending on the species. Altogether, our study highlights the functional versatility of LRGs across evolution, and reveals that functional conservation of orthologous LRGs may involve diversified mechanisms of action. These findings represent a striking example of how the evolvability of LRGs can provide adaptative flexibility to constrained gene regulatory networks.

+view abstract Nucleic acids research, PMID: 36727460 02 Feb 2023

Maskalenka K, Alagöz G, Krueger F, Wright J, Rostovskaya M, Nakhuda A, Bendall A, Krueger C, Walker S, Scally A, Rugg-Gunn PJ Epigenetics, Gene Targeting, Bioinformatics, Imaging

Gene duplication events can drive evolution by providing genetic material for new gene functions, and create opportunities for diverse developmental strategies to emerge between species. To study the contribution of duplicated genes to human early development, we examined the evolution and function of NANOGP1, a tandem duplicate of the transcription factor NANOG. We found that NANOGP1 and NANOG have overlapping but distinct expression profiles, with high NANOGP1 expression restricted to early epiblast cells and naïve-state pluripotent stem cells. Sequence analysis and epitope-tagging revealed that NANOGP1 is protein-coding with an intact homeobox domain. The duplication that created NANOGP1 occurred earlier in primate evolution than previously thought and has been retained only in great apes, whereas Old World monkeys have disabled the gene in different ways including homeodomain point mutations. NANOGP1 is a strong inducer of naïve pluripotency; however, unlike NANOG, it is not required to maintain the undifferentiated status of human naïve pluripotent cells. By retaining expression, sequence and partial functional conservation with its ancestral copy, NANOGP1 exemplifies how gene duplication and subfunctionalisation can contribute to transcription factor activity in human pluripotency and development.

+view abstract Development (Cambridge, England), PMID: 36621005 09 Jan 2023

von Meyenn F, Berrens RV, Andrews S, Santos F, Collier AJ, Krueger F, Osorno R, Dean W, Rugg-Gunn PJ, Reik W Epigenetics, Bioinformatics

n/a

+view abstract Developmental cell, PMID: 36473463 05 Dec 2022

Group Members

Peter Rugg-Gunn

Group Leader and Head of Public Engagement

Richard Acton

Data Outputs Manager

Adam Bendall

PhD Student

Louis Coussement

Visiting Student

Sarah Elderkin

Senior Research Scientist

Naoko Irie

Visiting Student

Andrew Malcolm

Postdoc Research Scientist

Matteo Mole

Postdoc Research Scientist

Thomas Owens

Research Assistant

Andrea Palomar

Visiting Scientist

Christopher Penfold

Postdoc Research Scientist

Maria Rostovskaya

Senior Research Scientist

Maria Santos Romero

Postdoc Research Scientist

Yang Wang

Postdoc Research Scientist

Amy Wilkinson

PhD Student

Thomas Willday

Research Assistant

Irene Zorzan

Postdoc Research Scientist