Regulation of early embryo development and pluripotency through alternative splicing

Regulation of early embryo development and pluripotency through alternative splicing

Lab members: Bárbara Pernaute, Chris Wyatt, Marta Miret, Victoria Rodríguez-Vaello, Thomas Spruce.

Funding: MINECO, Marie Skłodowska-Curie Actions, Boehringer Ingelheim, La Caixa, CRG.

Understanding how the differentiation potential of the mammalian embryo gets restricted during development is a key question in the embryology and stem cell fields. As with every developmental process, the loss of differentiation potential is expected to be caused by extensive transcriptome remodeling through transcriptional and post-transcriptional regulatory mechanisms. Among the latter, alternative splicing is the most prevalent in mammals, with over 90% of human genes being alternatively spliced. However, little is known regarding its role in modulating pluripotency and cell differentiation. The aim of this research line is to study the role that alternative splicing plays in these processes.


Exonic-centric view of mouse early development: from zygote to blastocyst (Barbara Pernaute)

The results obtained in this research line will provide novel insights into how alternative splicing impacts pluripotency and early embryo development. Thus, it will advance our understanding of how genetic networks from multiple regulatory layers control pluripotency and self-renewal in stem cells and in vivo, which is essential for their safe and effective use for therapeutic applications.

Related publications:

  • Maeso, I., Dunwell, T.L., Wyatt, C.D.R., Marlétaz, F., Veto, B., Bernal, J.A., Quah, S., Irimia, M., Holland, P.W.H. (2016). Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammals. BMC Biology, 14:45.
  • Han, H.*, Irimia, M.*, Ross P.J., Sung, H.K., Alipanahi, B., David, L., Golipour, A., Gabut, M., Michael, I.P., Nachma, E.N., Wang, E., Trcka, D., Thompson, T., O'Hanlon, D., Slobodeniuc, V., Barbosa-Morais, N.L., Burge, C.B., Moffat, J., Frey, B.J., Nagy, A., Ellis, J.,  Wrana, J.L, Blencowe, B.J. (2013). MBNL proteins repress embryonic stem-cell-specific alternative splicing and reprogramming. Nature, 498(7453):241-5.
  • Venables, J.P., Lapasset, L., Gadea, G., Fort, P., Klinck, R., Irimia, M., Vignal, E., Thibault, P., Prinos, P., Chabot, B., Abou Elela, S., Roux, P., Lemaitre, J.M., Tazi, J. (2013). MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation. Nature Commun, 4:2480.