Understanding the networks that regulate trophoblast stem cell renewal
Researchers at theBabraham Institute in collaboration with the Centre for Trophoblast Research, University of Cambridge, have begun to unpick the network of molecular interactions essential for trophoblast stem (TS) cells to maintain their self-renewal potential. TS cells are a stem cell population that provides a great research tool to study early processes in placental development as they can give rise to all the different cell types forming the placenta. The researchers' efforts focused on a master regulator of gene expression called Esrrb (oestrogen-related receptor beta). In mice, loss of Esrrb causes defects in placental development which means that a developing embryo cannot be supported. The researchers found that Esrrb is critical for TS cells to maintain their undifferentiated stem cell identity and once Esrrb gene expression was lost, TS cells differentiated into distinct cell types.
The research pieced together the regulatory network – how Esrrb itself is controlled, and the downstream molecular network that over which it resides to maintain the stem cell character of TS cells. In addition, this work was able to make comparisons between the role of Esrrb in TS cells and embryonic stem (ES) cells; in contrast to TS cells that reflect the placental lineage, ES cells form the embryo proper. The research findings, published today in the journal Nature Communications, presents how Esrrb plays a role in both ES and TS cells but with markedly different regulatory mechanisms and targets.
The research contributes to establishing a clearer picture of how early steps in the placentation process are regulated, which are critical for the progression of pregnancy ultimately to support development of a normal foetus.
Affiliated researchers (in author order):
Paulina A. Latos, postdoc research scientist, Hemberger group, Epigenetics programme and next generation research fellow, Centre for Trophoblast Research, University of Cambridge
Myriam Hemberger, group leader, Epigenetics programme, member of the Centre for Trophoblast Research, University of Cambridge
Hisham Mohammed, postdoc research scientist, Reik group, Epigenetics programme
David Oxley, Head of Mass Spectrometry facility
Tissue section of a mouse embryo 6.5 days after conception showing the developing embryonic and extra-embryonic compartments. The extra-embryonic compartment contains the Esrrb-expressing trophoblast stem-like cells. In a live embryo these cells would give rise to the future placenta to sustain the developing embryo.
Animal research statement:
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research presented here used cultured mouse trophoblast stem (TS) cells and not live animals.
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Latos & Hemberger et al. (2015) Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells. Nature Communications.