A gene which gives stem cells the ability to produce any other cell has been found to play a vital role in the development of early sex cells.
The research team used early mouse embryos which did not express the Nanog gene to see the effect on development of Primordial Germ Cells (PGCs), the very earliest sex cells which ultimately produce eggs or sperm.
Deletion of the Nanog gene in this way reduced PGC numbers 5-fold but it was still possible for the cells to produce functional eggs or sperm.
The team was led by CRM Group Leader Prof Ian Chambers who discovered the fundamental role of Nanog in supporting stem cell pluripotency, the ability to produce any type of cell in the human body.
In Embryonic Stem Cells, the effects of the Nanog gene are mediated in part by a second gene Essrb. The study found that introduction of the Essrb gene in the embryos which do not express Nanog restored sex cell numbers and led to fertile adult mice.
The study also examined the function of Nanog in Primordial Germ Cell Like Cells (PGCLCs) which can be grown in the laboratory and which allow access to the very earliest steps in germ cell development. This shows that Nanog was required at an early stage in development and that in PGCLC lacking Nanog, Esrrb could substitute for Nanog function.
Although its role in stem cell pluripotency has previously been well established, the role of Nanog and other Transcription Factor genes was not clear in the development in early sex cells.
Prof Chambers said,
“This work helps us understand how gene regulators like Nanog and Esrrb control the very earliest stages of sex cell development.”
Nanog is named after Tir nan Og the legendary “Land of the Ever-Young”. Prof Chambers and colleagues chose the name as the gene effectively makes stem cells immortal.
This work is published in the journal Cell Reports, and was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Councils (MRC), Wellcome Trust and James Baird Fund.
Zhang, Man et al. (2018). Esrrb Complementation Rescues Development of Nanog-Null Germ Cells. Cell Reports, Volume 22, Issue 2, 332 – 339. http://dx.doi.org/10.1016/j.celrep.2017.12.060