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

Establishment of mouse expanded potential stem cells.
Yang J, Ryan DJ, Wang W, Tsang JC, Lan G, Masaki H, Gao X, Antunes L, Yu Y, Zhu Z, Wang J, Kolodziejczyk AA, Campos LS, Wang C, Yang F, Zhong Z, Fu B, Eckersley-Maslin MA, Woods M, Tanaka Y, Chen X, Wilkinson AC, Bussell J, White J, Ramirez-Solis R, Reik W, Göttgens B, Teichmann SA, Tam PPL, Nakauchi H, Zou X, Lu L, Liu P

Mouse embryonic stem cells derived from the epiblast contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species.

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Nature, , 1476-4687, , 2017

PMID: 29019987

Single-cell epigenomics: Recording the past and predicting the future.
Kelsey G, Stegle O, Reik W

Single-cell multi-omics has recently emerged as a powerful technology by which different layers of genomic output-and hence cell identity and function-can be recorded simultaneously. Integrating various components of the epigenome into multi-omics measurements allows for studying cellular heterogeneity at different time scales and for discovering new layers of molecular connectivity between the genome and its functional output. Measurements that are increasingly available range from those that identify transcription factor occupancy and initiation of transcription to long-lasting and heritable epigenetic marks such as DNA methylation. Together with techniques in which cell lineage is recorded, this multilayered information will provide insights into a cell's past history and its future potential. This will allow new levels of understanding of cell fate decisions, identity, and function in normal development, physiology, and disease.

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Science (New York, N.Y.), 358, 1095-9203, 69-75, 2017

PMID: 28983045

Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation.
Mohammed H, Hernando-Herraez I, Savino A, Scialdone A, Macaulay I, Mulas C, Chandra T, Voet T, Dean W, Nichols J, Marioni JC, Reik W

The mouse inner cell mass (ICM) segregates into the epiblast and primitive endoderm (PrE) lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq) of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators. At E6.5, the transition from epiblast to primitive streak is linked with decreased expression of polycomb subunits, suggesting a key regulatory role. Notably, our analyses suggest elevated transcriptional noise at E3.5 and within the non-committed epiblast at E6.5, coinciding with exit from pluripotency. By contrast, E6.5 primitive streak cells became highly synchronized and exhibit a shortened G1 cell-cycle phase, consistent with accelerated proliferation. Our study systematically charts transcriptional noise and uncovers molecular processes associated with early lineage decisions.

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Cell reports, 20, 2211-1247, 1215-1228, 2017

PMID: 28768204

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Keywords

cell memory
dna
epigenetics
methylation
reprogramming

Group Members

Latest Publications

Establishment of mouse expanded potential stem cells.

Yang J, Ryan DJ, Wang W

Nature
1476-4687: (2017)

PMID: 29019987

Single-cell epigenomics: Recording the past and predicting the future.

Kelsey G, Stegle O, Reik W

Science (New York, N.Y.)
358 1095-9203:69-75 (2017)

PMID: 28983045

Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation.

Mohammed H, Hernando-Herraez I, Savino A

Cell reports
20 2211-1247:1215-1228 (2017)

PMID: 28768204

Epigenetic resetting of human pluripotency.

Guo G, von Meyenn F, Rostovskaya M

Development (Cambridge, England)
144 1477-9129:2748-2763 (2017)

PMID: 28765214

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