An organism’s body plan arises through a process called gastrulation, during which the embryo forms three distinct layers of cells that will later give rise to all organs. Now, FMI researchers have mapped the development of three-dimensional clusters of cells that mimic aspects of gastrulation, providing important insights into the molecular mechanisms that regulate early embryonic development and cell fate determination.
Scientists have succeeded in developing methods that use mouse embryonic stem cells to generate three-dimensional clusters of cells, called gastruloids, that recapitulate certain aspects of gastrulation in a lab dish. But little is known about the exact events that lead gastruloids to differentiate into specialized cell types and organize in a manner that resembles the early mouse body plan.
Using single-cell RNA sequencing and advanced imaging methods, researchers in Prisca Liberali ’s group mapped key developmental events in tens of thousands of gastruloids. The researchers found that between 48 and 72 hours of development, cells within the gastruloid core revert to an early stem-cell-like state, whereas those at the periphery show signs of developing a feature called the primitive streak, which is important to establish the embryo’s head-to-tail axis. Then, these two cell populations ’break symmetry’ and start to localize at opposing poles along the head-to-tail axis of the developing gastruloid.
The researchers also tested the effects of different compounds on thousands of gastruloids — work that revealed key networks of genes that regulate the main steps of gastruloid development. Leveraging findings from this analysis, the team developed an approach to generate gastruloids that better resemble neural and anterior foregut structures, which in the embryo give rise to cell types in tissues such as the esophagus, lung and thyroid.
The findings can help researchers to better understand how gastruloids develop and, more generally, how complex patterns emerge from a homogeneous population of cells, the researchers say.
Simon Suppinger*, Marietta Zinner*, Nadim Aizarani*, Ilya Lukonin*, Raphael Ortiz, Chiara Azzi, Michael B. Stadler, Stefano Vianello, Giovanni Palla, Hubertus Kohle, Alexandre Mayran, Matthias P. Lutolf, and Prisca Liberali Multimodal characterization of murine gastruloid development Cell Stem Cell (2023) Advance online publication
About the first authors
Simon Suppinger is a PhD candidate in the Liberali lab and hails from Austria. In his spare time, he likes running, hiking and visiting modern-art museums.
Marietta Zinner is a PhD graduate from the Liberali lab. She’s also from Austria and enjoys mountain biking, gardening, cooking and baking.
Nadim Aizarani was born in Lebanon and holds German citizenship. In his free time, he sings opera as well as modern music and musical theater.
Hailing from Estonia, Ilya Lukonin was a PhD candidate in the Liberali lab and then a research associate in the FMI’s Facility for Advanced Imaging and Microscopy. His hobbies include hiking and biking.