Peter Rugg-Gunn

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) in combination with a variety of molecular and genetic approaches to characterise and perturb their epigenomes. The stem cell models are sometimes complemented with the characterisation of mouse and human embryos at very early stages in their development.

This research is important because establishing our epigenomes correctly during development has long lasting consequences on our health, and we 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 abilitiy to drive their specialisation towards useful cell types, which are essential requirements to fulfill their promise in regenerative medicine. 

Latest Publications

Cell-Surface Proteomics Identifies Differences in Signaling and Adhesion Protein Expression between Naive and Primed Human Pluripotent Stem Cells.
Wojdyla K, Collier AJ, Fabian C, Nisi PS, Biggins L, Oxley D, Rugg-Gunn PJ

Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes. The lack of detailed information about cell-surface protein expression in these two pluripotent cell types prevents an understanding of how the cells communicate and interact with their microenvironments. Here, we used plasma membrane profiling to directly measure cell-surface protein expression in naive and primed hPSC. This unbiased approach quantified over 1,700 plasma membrane proteins, including those involved in cell adhesion, signaling, and cell interactions. Notably, multiple cytokine receptors upstream of JAK-STAT signaling were more abundant in naive hPSC. In addition, functional experiments showed that FOLR1 and SUSD2 proteins are highly expressed at the cell surface in naive hPSC but are not required to establish human naive pluripotency. This study provides a comprehensive stem cell proteomic resource that uncovers differences in signaling pathway activity and has identified new markers to define human pluripotent states.

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Stem cell reports, 1, 1, 10 Apr 2020

DOI: 10.1016/j.stemcr.2020.03.017

PMID: 32302559

Multi-omics profiling of mouse gastrulation at single-cell resolution.
Argelaguet R, Clark SJ, Mohammed H, Stapel LC, Krueger C, Kapourani CA, Imaz-Rosshandler I, Lohoff T, Xiang Y, Hanna CW, Smallwood S, Ibarra-Soria X, Buettner F, Sanguinetti G, Xie W, Krueger F, Göttgens B, Rugg-Gunn PJ, Kelsey G, Dean W, Nichols J, Stegle O, Marioni JC, Reik W

Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes. Global epigenetic reprogramming accompanies these changes, but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements at enhancer marks, driven by ten-eleven translocation (TET)-mediated demethylation and a concomitant increase of accessibility. By contrast, the methylation and accessibility landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or remodelled before cell-fate decisions, providing the molecular framework for a hierarchical emergence of the primary germ layers.

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Nature, 576, 7787, 2019

DOI: 10.1038/s41586-019-1825-8

PMID: 31827285

The application of cell surface markers to demarcate distinct human pluripotent states.
Goodwin J, Laslett AL, Rugg-Gunn PJ

Recent advances in human pluripotent stem cell (hPSC) research have uncovered different subpopulations within stem cell cultures and have captured a range of pluripotent states that hold distinct molecular and functional properties. At the two ends of the pluripotency spectrum are naïve and primed hPSC, whereby naïve hPSC grown in stringent conditions recapitulate features of the preimplantation human embryo, and the conventionally grown primed hPSC align closer to the early postimplantation embryo. Investigating these cell types will help to define the mechanisms that control early development and should provide new insights into stem cell properties such as cell identity, differentiation and reprogramming. Monitoring cell surface marker expression provides a valuable approach to resolve complex cell populations, to directly compare between cell types, and to isolate viable cells for functional experiments. This review discusses the discovery and applications of cell surface markers to study human pluripotent cell types with a particular focus on the transitions between naïve and primed states. Highlighted areas for future study include the potential functions for the identified cell surface proteins in pluripotency, the production of new high-quality monoclonal antibodies to naïve-specific protein epitopes and the use of cell surface markers to characterise subpopulations within pluripotent states.

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Experimental cell research, 0, 0, 30 Nov 2019

DOI: 10.1016/j.yexcr.2019.111749

PMID: 31790696