A human embryo at the four-cell stage. Image credit: Public domain
Embryos begin as a collection of similar cells, which progress in stages to form a huge variety of cell types in particular arrangements. These patterns of cells give rise to the different tissues and organs that make up the body.
Although we often use ‘model’ organisms such as mice and frogs to study how embryos develop, our species has evolved unique ways to control organ development. Investigating these processes is difficult: we cannot experiment on human embryos, and our development is hard to recreate in test tubes. As a result, we do not fully understand how developing human cells specialize and organize.
Libby et al. have now created a new system to study how different genes control cell organization. The system uses human pluripotent stem cells – cells that have the ability to specialize into any type of cell. Some of the stem cells are modified using a technique called inducible CRISPR interference, which makes it possible to reduce the activity of certain genes in these cells.
Libby et al. used this technique to investigate how changes to the activity of two genes – called ROCK1 and CDH1 – affect how a mixed group of stem cells organized themselves. Cells that lacked ROCK1 formed bands near the edges of the group. Cells that lacked CDH1 segregated themselves from other cells, forming ‘islands’ inside the main group. The cells retained their ability to specialize into any type of cell after forming these patterns. However, specific groups of cells were more likely to become certain cell types.
The method developed by Libby et al. can be used to study a range of complex tissue development and cell organization processes. Future work could create human tissue model systems for research into human disease or drug development.
