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

Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment.
Kirschner K, Chandra T, Kiselev V, Flores-Santa Cruz D, Macaulay IC, Park HJ, Li J, Kent DG, Kumar R, Pask DC, Hamilton TL, Hemberg M, Reik W, Green AR

Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and observed an expansion of the p53-positive subpopulation in old mice. Our results reveal cellular heterogeneity in the onset of HSC aging and implicate a role for JAK2V617F-driven proliferation in the p53-mediated functional decline of old HSCs.

+ View Abstract

Cell reports, 19, 2211-1247, 1503-1511, 2017

PMID: 28538171

A MILI-independent piRNA biogenesis pathway empowers partial germline reprogramming.
Vasiliauskaitė L, Vitsios D, Berrens RV, Carrieri C, Reik W, Enright AJ, O'Carroll D

In mice, the pathway involving PIWI and PIWI-interacting RNA (PIWI-piRNA) is essential to re-establish transposon silencing during male-germline reprogramming. The cytoplasmic PIWI protein MILI mediates piRNA-guided transposon RNA cleavage as well as piRNA amplification. MIWI2's binding to piRNA and its nuclear localization are proposed to be dependent upon MILI function. Here, we demonstrate the existence of a piRNA biogenesis pathway that sustains partial MIWI2 function and reprogramming activity in the absence of MILI.

+ View Abstract

Nature structural & molecular biology, , 1545-9985, , 2017

PMID: 28530707

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.

+ View Abstract

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

PMID: 28399939

01223 496336

Email Wolf
View Profile

Keywords

cell memory
dna
epigenetics
methylation
reprogramming

Group Members

Latest Publications

Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment.

Kirschner K, Chandra T, Kiselev V

Cell reports
19 2211-1247:1503-1511 (2017)

PMID: 28538171

A MILI-independent piRNA biogenesis pathway empowers partial germline reprogramming.

Vasiliauskaitė L, Vitsios D, Berrens RV

Nature structural & molecular biology
1545-9985: (2017)

PMID: 28530707

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