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Reik Group

Reik Group
Reik Group
Wolf Reik
Honorary Group Leader
Reik Group

Research Summary

Our lab is interested in epigenetic gene regulation in mammalian development and in ageing. Global epigenetic reprogramming occurs at fertilisation and fundamentally remodels the epigenomes of sperm and egg. We are working to understand the mechanisms of reprogramming and also how it may be linked with zygotic genome activation, the sudden transcriptional springing to life of the genome in the early embryo.

Soon after implantation of the embryo in the maternal uterus there is a major programme of cell fate decisions which establishes the three primary germ layers, the ectoderm (which gives rise to brain and skin), the mesoderm (giving rise to muscle and heart), and the endoderm (which gives rise to the gut amongst other tissues).

These three lineages are the foundations of all organs in the adult body and we are interested in the transcriptional and epigenetic events that underlie their emergence from the undifferentiated epiblast. Finally, we are studying how the epigenome degrades during ageing potentially in a programmed fashion, and whether there are approaches by which this degradation can be slowed down or reversed.

Latest Publications

Open Access
Corujo-Simon E, Bates LE, Yanagida A, Jones K, Clark S, von Meyenn F, Reik W, Nichols J Epigenetics

To implant in the uterus, mammalian embryos form blastocysts comprising trophectoderm (TE) surrounding an inner cell mass (ICM), confined to the polar region by the expanding blastocoel. The mode of implantation varies between species. Murine embryos maintain a single layered TE until they implant in the characteristic thick deciduum, whereas human blastocysts attach via polar TE directly to the uterine wall. Using immunofluorescence (IF) of rapidly isolated ICMs, blockade of RNA and protein synthesis in whole embryos, or 3D visualization of immunostained embryos, we provide evidence of multi-layering in human polar TE before implantation. This may be required for rapid uterine invasion to secure the developing human embryo and initiate formation of the placenta. Using sequential fluorescent labeling, we demonstrate that the majority of inner TE in human blastocysts arises from existing outer cells, with no evidence of conversion from the ICM in the context of the intact embryo.

+view abstract Developmental cell, PMID: 38889726

Open Access
Shah P, Hill R, Dion C, Clark SJ, Abakir A, Willems J, Arends MJ, Garaycoechea JI, Leitch HG, Reik W, Crossan GP Epigenetics

Mutations in DNA damage response (DDR) factors are associated with human infertility, which affects up to 15% of the population. The DDR is required during germ cell development and meiosis. One pathway implicated in human fertility is DNA translesion synthesis (TLS), which allows replication impediments to be bypassed. We find that TLS is essential for pre-meiotic germ cell development in the embryo. Loss of the central TLS component, REV1, significantly inhibits the induction of human PGC-like cells (hPGCLCs). This is recapitulated in mice, where deficiencies in TLS initiation (Rev1 or Pcna) or extension (Rev7 ) result in a > 150-fold reduction in the number of primordial germ cells (PGCs) and complete sterility. In contrast, the absence of TLS does not impact the growth, function, or homeostasis of somatic tissues. Surprisingly, we find a complete failure in both activation of the germ cell transcriptional program and in DNA demethylation, a critical step in germline epigenetic reprogramming. Our findings show that for normal fertility, DNA repair is required not only for meiotic recombination but for progression through the earliest stages of germ cell development in mammals.

+view abstract Nature communications, PMID: 38702312

Open Access
Agostinho de Sousa J, Wong CW, Dunkel I, Owens T, Voigt P, Hodgson A, Baker D, Schulz EG, Reik W, Smith A, Rostovskaya M, von Meyenn F Epigenetics

Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine. Naïve hPSCs hold promise to overcome some of the limitations of conventional (primed) hPSCs, including recurrent epigenetic anomalies. Naïve-to-primed transition (capacitation) follows transcriptional dynamics of human embryonic epiblast and is necessary for somatic differentiation from naïve hPSCs. We found that capacitated hPSCs are transcriptionally closer to postimplantation epiblast than conventional hPSCs. This prompted us to comprehensively study epigenetic and related transcriptional changes during capacitation. Our results show that CpG islands, gene regulatory elements, and retrotransposons are hotspots of epigenetic dynamics during capacitation and indicate possible distinct roles of specific epigenetic modifications in gene expression control between naïve and primed hPSCs. Unexpectedly, PRC2 activity appeared to be dispensable for the capacitation. We find that capacitated hPSCs acquire an epigenetic state similar to conventional hPSCs. Significantly, however, the X chromosome erosion frequently observed in conventional female hPSCs is reversed by resetting and subsequent capacitation.

+view abstract Science advances, PMID: 37774033

Group Members

Wolf Reik

Honorary Group Leader

Jonathan Boudeman

PhD Student

Yongmin Kwon

PhD Student

Annalisa Mupo

Visiting Scientist