Since I was an undergraduate student at the Veterinary School in Milan, and throughout the rest of my scientific career, I have been fascinated with the complexities of mammalian preimplantation development. That’s why the publication of our recent paper “Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development” feels like the natural conclusion of a long journey that started with buckets of cow ovaries in Italy, and ended with a collective effort shared by our team in the Stem Cell Bank at the Center for Regenerative Medicine in Barcelona (CMR[B]), under the direction of Drs Izpisua Belmonte and Veiga.
In just hours, the newly formed mammalian embryo terminates the program of the two gametes that formed it, escapes apoptosis, remodels its chromatin to a functional state, starts dividing, and turns on its genome while using up the reserves of protein and RNA inherited from mum (and dad, a little). This last process, termed embryonic genome activation (EGA), represents one of the first signs of “independent life” of a new individual.
As much as the researchers at the CMR[B] are used to manipulating embryos and work with tiny amount of material, studying preimplantation processes in general, and EGA in particular, is a great challenge in our species, as embryos are very scarce, heterogeneous in quality, and RNA amplification methods almost invariably introduce a very significant bias in downstream data quality. An incredible opportunity to look into details of this process came as the CMR[B] established a collaboration with Herbert Auer of the University of Barcelona. His facility just recently validated a method to amplify very small amount of RNA without bias, and we proceeded to apply this “pico-profiling” to a very detailed time course of single human embryos.
Among the many complex interactions that our study has unveiled, one certainly stands out: the human embryo starts EGA one full day before we thought since seminal works were published more than 30 years ago (Braude et al, 1988). Using a combination of extremely reliable transcriptional profiling and de novo transcription inhibition by amanitin treatment, we have been able to show that the human embryo transcribes from its own genome as early as the 2-cell stage (about 30hr after fertilization).
In order to make our data genome-wide expression data easily available to the scientific community at large we have prepared a free online database, HuMER (Human Embryo Resource; http://intranet.cmrb.eu/Human_embryos/home.html). It is our hope and desire that this resource would help us improve our ability to draw interdisciplinary connections between biological events and, in the process, increase our understanding of preimplantation development.
Written by first author of the paper, Dr. Rita Vassena.
Vassena, R., Boue, S., Gonzalez-Roca, E., Aran, B., Auer, H., Veiga, A., & Belmonte, J. (2011). Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development Development, 138 (17), 3699-3709 DOI: 10.1242/dev.064741