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Department of Physiology, Development and Neuroscience

 

Research

Mammalian germ cells, pluripotency and epigenesis

We are interested in how the mammalian germ cell lineage is established, and how it is programmed towards generating the totipotent state. We are also interested in how the pluripotent state is established during early development, and the mechanisms that regulate initiation of cell fate decisions. In particular, we are investigating the molecular basis of PGC specification for which Prdm1, Prdm14 and Tcfap2c constitute a tripartite genetic network. These regulators initiate extensive epigenetic reprogramming, including global DNA demethylation. For these studies, we use in vivo approaches, and cell-based systems for generating PGC-like states using pluripotent stem cells

Epigenetic programming in PGCs is a key property, which includes extensive histone modifications and higher order changes in nuclear organisation. PGCs eventually reach the epigenetic ground state with unprecedented global DNA demethylation, during which Tet1 and Tet2 play an important but not an exclusive role.

We are also investigating the relationship between germ cells and pluripotent stem cells, in which some genes, (eg: Prdm14) play a pivotal role in inducing a ground state of pluripotency and promote transitions through epigenetic barriers during reprogramming. We are interested in exploring how mechanistic insights from studies on germ cells may be used for manipulating cell fates and for rejuvenation of somatic cells.

Co-workers

Dang Vinh Do
Lynn Froggett
Wolfram Gruhn
Ufuk Gunesdogan
Jamie Hackett
Yun Huang
Naoko Irie
Elena Itskovich
Shinseog Kim
Toshihiro Kobayashi
Caroline Lee
Chris Penfold
Roopsha Sengupta
Anastasiya Sybirna
Walfred Tang
Julia Tischler
Freddy Wong

Publications

Key publications: 

Tang F, Barbacioru C, Bao S, Lee C, Nordman E, Xiaohui W, Lao K, Surani MA, (2015), Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-seq analysis, Cell Stem Cell, 5 6(5-2) 468-478

Irie N, Weinberger, Tang WWC, Kobayashi T, Viukov S, Manor Y, Dietmann S, Hanna JH, Surani MA, (2015), SOX17 is a critical specifier of human primordial germ cell fate, Cell, 160, 253-268

Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA, Surani MA, (2012), Germline DNA demethylation dynamics and imprint erasure through 5-hydoxymethylcytosine, Science, 339, 448-452

 

 

Director of Germline and Epigenomics Research
 Picture of Azim  Surani

Contact Details

+44 (0) 1223 334088