We have decided to start this page as a reference for those who have an interest in using our polarized embryoid body system that we called â€˜Gastruloidsâ€™1-3. This experimental system was inspired by the work of Y. Marikawa with Embryoid bodies derived from P19 cells4,5 and we see them as a useful tool to investigate the principles underlying early mammalian development6. Importantly we believe that they can be used to learn how to engineer tissues and organs, exemplified in the following two ways. Firstly, given that we know a great deal about early mammalian development, it allows us to attempt to replicate developmental processes in culture and to understand what it takes to do so. Secondly, as early embryonic development can be a platform for the generation of niches of adult stem cells, thusly, as the research progresses we might find ourselves using Gastruloids to engineer the seeds of adult tissues.
In this page you will have access to our protocols, experimental details, improvements and results; we also hope to receive feedback. If we are to make good of this model system, we need to develop it as an open community resource. An important goal of this work (and, we presume, that of the broader organoid field) is to achieve reproducibility, because we believe that, much as in engineering7, this means that there is some understanding of the mechanisms that mediate the processes that mediate the outcome, in this case, specific tissues and organs.
So, here we start and look forward to your feedback.
- van den Brink, S.C., Baillie-Johnson, P., Balayo, T., Hadjantonakis, A.K., Nowotschin, S., Turner, D.A. & Martinez Arias, A. Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells. Development 141, 4231-4242 (2014).
- Turner, D.A., Rue, P., Mackenzie, J.P., Davies, E. & Martinez Arias, A. Brachyury cooperates with Wnt/Î²-Catenin signalling to elicit Primitive Streak-like behaviour in differentiating mouse ES cells. BMC Biol 12, 63 (2014).
- Baillie-ÂJohnson, P., van den Brink, S., Balayo, T., Turner, D.A. & Martinez Arias, A. Generation of aggregates of mouse ES cells that show symmetry breaking, polarisation and emergent collective behaviour. JOVE (2014).
- Marikawa, Y., Tamashiro, D.A., Fujita, T.C. & Alarcon, V.B. Aggregated P19 mouse embryonal carcinoma cells as a simple in vitro model to study the molecular regulations of mesoderm formation and axial elongation morphogenesis. Genesis 47, 93-106 (2009).
- Li, A.S. & Marikawa, Y. An in vitro gastrulation model recapitulates the morphogenetic impact of pharmacological inhibitors of developmental signaling pathways. Mol Reprod Dev 82, 1015-1036 (2015).
- Turner, D.A., Baillie-Johnson, P. & Martinez Arias, A. Organoids and the genetically encoded self-assembly of embryonic stem cells. Bioessays 38, 181-191 (2016).
- Gjorevski, N., Ranga, A. & Lutolf, M.P. Bioengineering approaches to guide stem cell-based organogenesis. Development 141, 1794-1804 (2014)