Transcription Factors Interplay Key to Inducing Germ Cells

A new paper in Stem Cell Reports demonstrates the interplay between transcription factors at the early stages of development of germ cells, the cells that go on to form the precursors of sperm and eggs.

Primordial germ cells (PGCs) are the precursors of gametes, so they are vital for germline development and sexual reproduction. The identity of cells, including PGCs, is controlled by transcription factors which control which genes are switched on and off. PGCs develop because of specific signals, mainly from a protein called bone morphogenic factor 4 (BMP4) and other cytokines, which are small proteins important for the growth and activity of cells. The latest article from Professor Ian Chambers, Matus Vojtek and colleagues explores the interplay of transcription factors occurring at the earliest stages of cells becoming Primordial Germ Cells (PGC specification).

The process of PGC specification can be replicated in the lab using epiblast-like cells (EpiLCs) and exposing them to cytokines. However, the requirement for cytokines is removed if the transcription factor NANOG is expressed. Named by Professor Chambers after Tir nan Og the legendary “Land of the Ever-Young”, NANOG is so-called because the gene makes embryonic stem cells immortal. Vojtek and colleagues investigated the levels of various transcription factors expressed throughout early stages of PGC development and over-expressed them to explore how NANOG can induce differentiation of PGCs.

The research team found that the way that NANOG induces specification of PGCs is by repressing the transcription factor OTX2. Sustained OTX2 expression was shown to prevent NANOG-induced differentiation. They also found that although the transcription factor ESRRB performs a similar role to NANOG in other cell types, ESRRB cannot repress OTX2 and so, cannot induce PGC specification unless the OTX2 expression is reduced by half.

This research has been published in the journal Stem Cell Reports and was supported by funding from the Biotechnology and Biological Sciences Research Council, the Medical Research Council of the United Kingdom and the National Natural Science Foundation of China.

The full article can be read here. 

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