Study identifies the emergence and progression of factors that drive embryonic pluripotency
Researchers at EMBL-EBI and the University of Cambridge have pinpointed the factors that regulate pluripotency during early embryogenensis in mammals
Researchers at EMBL’s European Bioinformatics Institute (EMBL-EBI) and the Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge (UK) have identified factors that induce the formation of pluripotent cells. The study sheds light on human embryonic development helping research in cell reprogramming and assisted conception.
Stem cells are widely known for their pluripotency – a short lived state in embryos, it is essential to normal development. In this study, the researchers mapped the time and location of genes that were expressed during early development of the mouse and common marmoset, a nonhuman primate species. This permitted them to pinpoint the changes that regulate pluripotency in both mammals. They continued by analyzing the complex network of gene regulation that supports pluripotency, looking closely at how this network comes together and later collapses as cells exit the pluripotent state to differentiate.
“Our goal was to generate a comprehensive map of gene expression in the early stages of embryogenesis in the mouse, which has traditionally been the best model for mammalian development, and to see how that knowledge could be translated to primates,” explained Paul Bertone from the Wellcome Trust–MRC Stem Cell Institute.
To compare pluripotent cells in rodents and primates, single-cell RNA sequencing on small clusters of cells (8-20 cells) was utilized to establish precise gene-expression patterns for specific stages of early development. This resulted in a framework for understanding the emergence and progression of pluripotency in different mammals.
“Many of the genes that give rise to the pluripotent identity in mice were also expressed in marmoset, demonstrating a common foundation for pluripotency in mammals,” commented Austin Smith, also of the Stem Cell Institute. “But there were some differences in signaling pathways between the two species, indicating that lineage specification in primates is not entirely conserved.”
“We found that WNT signaling in the marmoset is critical for normal differentiation of one of the first three cell lineages to emerge,” continued Paul. “Inhibiting this pathway has a profound effect – one of those lineages is subsumed by pluripotent cells rather than forming correctly. It will be interesting to see through in vitro studies whether WNT and perhaps other pathways are similarly utilized in humans.”
The results are a valuable resource for identifying the factors and pathways that regulate pluripotency in different mammals. The findings can also be used to optimize embryonic stem-cell derivation and reprogramming, in cell cultures. The knowledge gained will help researchers understand early lineage decisions in embryonic cells, potentially leading to improved methods for human blastocyst development for assisted conception.
Sources: www.ebi.ac.uk/about/news/press-releases/unpacking-embryonic-pluripotency; Boroviak T, Loos R, Lombard P et al. Lineage-specific profiling delineates the emergence and progression of naive pluripotency in mammalian embryogenesis. Dev. Cell doi:10.1016/j.devcel.2015.10.011 (2015) (Epub ahead of print).