Azim Surani PhD CBE FRS FMedSci, Director of Germline and Epigenomics Research, Member of the Physiology, Development and Neuroscience Department.
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 (Fig 1). We are also interested in how the pluripotent state is established during early development, and the mechanisms that regulate initiation of cell fate decisions (Fig 2). 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 (Fig 3).
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.
• Gillich A, Bao S, Grabole N, Hayashi K, Trotter MW, Pasque V, Magnusdottir E and Surani MA (2012) Epiblast stem cell-based system reveals reprogramming synergy of germline factors. Cell Stem Cell , 10, 425-439
• Bao S, Leitch H, Gillich A, Nichols J, Tang F, Kim S, Lee C, Zwaka T, Li X and Surani MA (2012) The germ cell determinant Blimp1 is not required for derivation of pluripotent stem cells. Cell Stem Cell, 11, 110-117
•Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA and Surani MA (2012) Germline DNA demethylation dynamics and imprint erasure through 5-hydoxymethylcytosine. Science, 339, 448-452