Summary

During embryo development, humans and other animals with backbones (called vertebrates) repeatedly grow pairs of segments along the major body axis that runs from the head to the tail of the embryo. These segments, called somites, will later give rise to parts of the skeleton, as well as the associated muscle, cartilage, tendons and skin. Most of what we know about how these segments form during animal development comes from studies in chicken, fish (zebrafish), and mice. Because this process is highly complex and dynamic in nature, researchers need to observe this process while it is happening. However, it is quite difficult to do in mammals (which are part of the group of vertebrate animals) such as mice and impossible in humans.

To date, we know very little about how the process of segment formation happens in humans since there is no experimental way we can directly observe this process. We also don’t know how similar segment formation is compared to other vertebrate animals that we were able to study in more detail. This process is important to understand because when it goes wrong, it can lead to an abnormal curvature in the spine at birth, which affects about 1 in 10,000 newborns.

To recapitulate human segment formation in a dish, we used stem cells, which are capable of making any cell type in the body. To mimic the process that normally occurs in the embryo, we first let a defined number of stem cells form a cluster of cells (aggregate). Then we guided the stem cells to differentiate (change from a less specialized cell type to a more specialized cell type) to cell types that make up somites in the embryo. This differentiation process is highly regulated and typically happens without problems in the embryo. However, the process in a dish is much less well controlled. We systematically tested many conditions to figure out a way to reproducibly make 3D tissue structures (called organoids) that form somites from human stem cells. We also confirmed that the organization and size of somites, as well as the genes they turn on and off are very similar to what we know about vertebrate somites.

This new model of human segment formation is the first model of its kind which now allows us and other researchers to better understand how segments form in humans. It might also allow researchers to investigate what exactly goes wrong when vertebrae fail to form completely or when they fuse together causing a sideway curvature in newborns.

Publication

Budjan, C., Liu, S., Ranga, A., Gayen, S., Pourquié, O. and Hormoz, S. (2022). Paraxial mesoderm organoids model development of human somites. eLife 11. doi: 10.7554/eLife.68925