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21.01.16 Surani group discover role for NANOG alone in germ cell induction

last modified Jan 27, 2016 10:57 AM
In a Letter to Nature, the Surani lab show that the transcription factor NANOG can act alone to induce primordial germ cells from mouse epiblast-like cells in culture
21.01.16 Surani group discover role for NANOG alone in germ cell induction

Figure 1 from the paper: day-4 male PGCLCs

NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers

Murakami K., Günesdogan, U. et al. (2016) Nature 529, 403–407 (Published online 11 January 2016)



The Surani lab made an unexpected discovery that the transcription factor NANOG alone can induce mouse epiblast-like cells in culture to form primordial germ-cell (PGC)-like cells. NANOG is known to be a core pluripotency factor in the early formation of the embryo.    

PGCs give rise to sperm and eggs. They arise during development after implantation of the embryo in the epiblast. This developmental process can be studied in a culture dish (in vitro), where naive pluripotent mouse embryonic stem (ES) cells are directed to develop as epiblast-like cells, from which they can further progress to a PGC-like fate. It is known that a key signalling molecule called bone morphogenetic protein 4 (BMP4) can induce PGC-like cells in epiblast-like cells, but not in ES cells, by inducing expression of the key regulators of germ cell fate. The researchers, however, made an unexpected discovery that Nanog alone and without BMP4 can induce PGC-like cells in epiblast-like cells .

The researchers propose that after the ES cells lose their property of naive pluripotency during establishment of epiblast-like cells, changes take place in the chemical modifications of the cells' DNA (the epigenome). This resetting of the epigenome directs the binding of NANOG to regulatory DNA sequences to enhance or prevent the activity of particular sets of genes, allowing the cell to develop along a specified pathway, or fate.

The team shows that there is a marked change in the NANOG-binding pattern across the genome between the stages of ES cells and epiblast-like cells, suggesting that there is indeed an epigenetic resetting of regulatory elements at this point in the cell's trajectory from a naive pluripotent state to a more specified state.

The scientists propose a broadly applicable principle of how cells acquire the ability to give rise to distinct cell types, resulting from a context-dependent role of key transcription factors during development. The underlying mechanism might also explain how some transcription factors with key roles during development can also promote human diseases in a different context. 


More information about the Surani lab.

Studying development to understand disease

The Gurdon Institute is funded by the Wellcome Trust and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.