Life Sciences Research for Lifelong Health

Wolf Reik

Research Summary

Epigenetic modifications such as DNA methylation and histone marks are often relatively stable in differentiated and in adult tissues in the body, where they help to confer a stable cell identity on tissues. The process of epigenetic reprogramming, by which many of these marks are removed from DNA, is important for the function of embryonic stem cells and in reprogramming stem cells from adult tissue cells. When this erasure goes wrong there may be adverse consequences for healthy development and ageing, which can potentially extend over more than one generation.

​Our insights into the mechanisms of epigenetic reprogramming may help with developing better strategies for stem cell therapies and to combat age related decline. We have also recently initiated work on epigenetic regulation of social behaviours in insects, where we are interested in how patterning and regulation of DNA methylation in the brain is linked with the evolution of sociality.

Latest Publications

Multi-tissue DNA methylation age predictor in mouse.
Stubbs TM, Bonder MJ, Stark AK, Krueger F, von Meyenn F, Stegle O, Reik W

DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse.

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Genome biology, 18, 1474-760X, 68, 2017

PMID: 28399939

DeepCpG: accurate prediction of single-cell DNA methylation states using deep learning.
Angermueller C, Lee HJ, Reik W, Stegle O

Recent technological advances have enabled DNA methylation to be assayed at single-cell resolution. However, current protocols are limited by incomplete CpG coverage and hence methods to predict missing methylation states are critical to enable genome-wide analyses. We report DeepCpG, a computational approach based on deep neural networks to predict methylation states in single cells. We evaluate DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols. DeepCpG yields substantially more accurate predictions than previous methods. Additionally, we show that the model parameters can be interpreted, thereby providing insights into how sequence composition affects methylation variability.

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Genome biology, 18, 1474-760X, 67, 2017

PMID: 28395661

Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism.
Hahn O, Grönke S, Stubbs TM, Ficz G, Hendrich O, Krueger F, Andrews S, Zhang Q, Wakelam MJ, Beyer A, Reik W, Partridge L

Dietary restriction (DR), a reduction in food intake without malnutrition, increases most aspects of health during aging and extends lifespan in diverse species, including rodents. However, the mechanisms by which DR interacts with the aging process to improve health in old age are poorly understood. DNA methylation could play an important role in mediating the effects of DR because it is sensitive to the effects of nutrition and can affect gene expression memory over time.

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Genome biology, 18, 1474-760X, 56, 2017

PMID: 28351387

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Keywords

cell memory
dna
epigenetics
methylation
reprogramming

Group Members

Latest Publications

Multi-tissue DNA methylation age predictor in mouse.

Stubbs TM, Bonder MJ, Stark AK

Genome biology
18 1474-760X:68 (2017)

PMID: 28399939

DeepCpG: accurate prediction of single-cell DNA methylation states using deep learning.

Angermueller C, Lee HJ, Reik W

Genome biology
18 1474-760X:67 (2017)

PMID: 28395661

SC3: consensus clustering of single-cell RNA-seq data.

Kiselev VY, Kirschner K, Schaub MT

Nature methods
1548-7105: (2017)

PMID: 28346451

DNA methylation homeostasis in human and mouse development.

Iurlaro M, von Meyenn F, Reik W

Current opinion in genetics & development
43 1879-0380:101-109 (2017)

PMID: 28260631

The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice.

Langie SA, Cameron KM, Ficz G

Genes
8 : (2017)

PMID: 28218666

Tracking the embryonic stem cell transition from ground state pluripotency.

Kalkan T, Olova N, Roode M

Development (Cambridge, England)
1477-9129: (2017)

PMID: 28174249

Gender Differences in Global but Not Targeted Demethylation in iPSC Reprogramming.

Milagre I, Stubbs TM, King MR

Cell reports
18 2211-1247:1079-1089 (2017)

PMID: 28147265

A Hox-Embedded Long Noncoding RNA: Is It All Hot Air?

Selleri L, Bartolomei MS, Bickmore WA

PLoS genetics
12 1553-7404:e1006485 (2016)

PMID: 27977680

Efficient targeted DNA methylation with chimeric dCas9-Dnmt3a-Dnmt3L methyltransferase.

Stepper P, Kungulovski G, Jurkowska RZ

Nucleic acids research
1362-4962: (2016)

PMID: 27899645

The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy.

Thienpont B, Aronsen JM, Robinson EL

The Journal of clinical investigation
1558-8238: (2016)

PMID: 27893464