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

Voices in methods development.
Anikeeva P, Boyden E, Brangwynne C, Cissé II, Fiehn O, Fromme P, Gingras AC, Greene CS, Heard E, Hell SW, Hillman E, Jensen GJ, Karchin R, Kiessling LL, Kleinstiver BP, Knight R, Kukura P, Lancaster MA, Loman N, Looger L, Lundberg E, Luo Q, Miyawaki A, Myers EW, Nolan GP, Picotti P, Reik W, Sauer M, Shalek AK, Shendure J, Slavov N, Tanay A, Troyanskaya O, van Valen D, Wang HW, Yi C, Yin P, Zernicka-Goetz M, Zhuang X

Nature methods, 16, 1548-7105, 945-951, 2019

PMID: 31562479

Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in mouse muscle stem cells.
Hernando-Herraez I, Evano B, Stubbs T, Commere PH, Jan Bonder M, Clark S, Andrews S, Tajbakhsh S, Reik W

Age-related tissue alterations have been associated with a decline in stem cell number and function. Although increased cell-to-cell variability in transcription or epigenetic marks has been proposed to be a major hallmark of ageing, little is known about the molecular diversity of stem cells during ageing. Here we present a single cell multi-omics study of mouse muscle stem cells, combining single-cell transcriptome and DNA methylome profiling. Aged cells show a global increase of uncoordinated transcriptional heterogeneity biased towards genes regulating cell-niche interactions. We find context-dependent alterations of DNA methylation in aged stem cells. Importantly, promoters with increased methylation heterogeneity are associated with increased transcriptional heterogeneity of the genes they drive. These results indicate that epigenetic drift, by accumulation of stochastic DNA methylation changes in promoters, is associated with the degradation of coherent transcriptional networks during stem cell ageing. Furthermore, our observations also shed light on the mechanisms underlying the DNA methylation clock.

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Nature communications, 10, 2041-1723, 4361, 2019

PMID: 31554804

Distinct Molecular Trajectories Converge to Induce Naive Pluripotency.
Stuart HT, Stirparo GG, Lohoff T, Bates LE, Kinoshita M, Lim CY, Sousa EJ, Maskalenka K, Radzisheuskaya A, Malcolm AA, Alves MRP, Lloyd RL, Nestorowa S, Humphreys P, Mansfield W, Reik W, Bertone P, Nichols J, Göttgens B, Silva JCR

Understanding how cell identity transitions occur and whether there are multiple paths between the same beginning and end states are questions of wide interest. Here we show that acquisition of naive pluripotency can follow transcriptionally and mechanistically distinct routes. Starting from post-implantation epiblast stem cells (EpiSCs), one route advances through a mesodermal state prior to naive pluripotency induction, whereas another transiently resembles the early inner cell mass and correspondingly gains greater developmental potency. These routes utilize distinct signaling networks and transcription factors but subsequently converge on the same naive endpoint, showing surprising flexibility in mechanisms underlying identity transitions and suggesting that naive pluripotency is a multidimensional attractor state. These route differences are reconciled by precise expression of Oct4 as a unifying, essential, and sufficient feature. We propose that fine-tuned regulation of this "transition factor" underpins multidimensional access to naive pluripotency, offering a conceptual framework for understanding cell identity transitions.

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Cell stem cell, , 1875-9777, , 2019

PMID: 31422912

Group Members

Latest Publications

Voices in methods development.

Anikeeva P, Boyden E, Brangwynne C

Nature methods
16 1548-7105:945-951 (2019)

PMID: 31562479

Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in mouse muscle stem cells.

Hernando-Herraez I, Evano B, Stubbs T

Nature communications
10 2041-1723:4361 (2019)

PMID: 31554804

Distinct Molecular Trajectories Converge to Induce Naive Pluripotency.

Stuart HT, Stirparo GG, Lohoff T

Cell stem cell
1875-9777: (2019)

PMID: 31422912

Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1.

Martin-Herranz DE, Aref-Eshghi E, Bonder MJ

Genome biology
20 1474-760X:146 (2019)

PMID: 31409373

Establishment of porcine and human expanded potential stem cells.

Gao X, Nowak-Imialek M, Chen X

Nature cell biology
21 1476-4679:687-699 (2019)

PMID: 31160711

TET3 prevents terminal differentiation of adult NSCs by a non-catalytic action at Snrpn.

Montalbán-Loro R, Lozano-Ureña A, Ito M

Nature communications
10 2041-1723:1726 (2019)

PMID: 30979904

A single-cell molecular map of mouse gastrulation and early organogenesis.

Pijuan-Sala B, Griffiths JA, Guibentif C

Nature
1476-4687: (2019)

PMID: 30787436

Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program.

Eckersley-Maslin M, Alda-Catalinas C, Blotenburg M

Genes & development
33 1549-5477:194-208 (2019)

PMID: 30692203

Transcriptional Heterogeneity in Naive and Primed Human Pluripotent Stem Cells at Single-Cell Resolution.

Messmer T, von Meyenn F, Savino A

Cell reports
26 2211-1247:815-824.e4 (2019)

PMID: 30673604

The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome.

Gdula MR, Nesterova TB, Pintacuda G

Nature communications
10 2041-1723:30 (2019)

PMID: 30604745