New advances in stem-cell derived mouse embryo model
A day 8 stem cell-derived mouse embryo with developing brain and heart regions. Credit: Kasey Lau for the Zernicka-Goetz laboratory

Two weeks after announcing the development of a mouse embryo model complete with beating hearts and the foundations for a brain and other organs from mouse stem cells, researchers in the lab of a professor have published new findings. The embryo model is easier to adopt in other laboratories as a result of this modification.

There is a new study in the journal. Two graduate students from the University of Cambridge and the Weizmann Institute of Science were involved in the research.

"This discovery opens up new avenues for understanding why the majority of human pregnancies are lost and to create knowledge that will prevent this from happening," says Zernicka-Goetz, who is also a professor of mammal development and stem cell biology. With this knowledge, we will be able to repair tissues and organs more effectively than we can now.

Video showing beating movements of the developing heart regions in a day 8 stem cell-derived mouse embryo. Credit: Kasey Lau for the Zernicka-Goetz laboratory

"As we develop these models further, we will learn more about the signals that initiate and guide the development of organs, which will give us routes for helping to generate organs in culture that will ultimately find application in transplant surgery or in regeneration medicine," she says.

In a paper published in the journal Nature on August 25, the team showed how to create a mouse embryo model out of stem cells. The team guided three populations of stem cells to interact, inducing the expression of certain genes and establishing an environment for the cells to talk to each other. The stem cells self-organized into structures that then progressed through successive development stages until the mouse embryo model had beating hearts and the foundations for a brain and all other organs. This is the most advanced stage of development so far.

In the first few days after fertilization, there are three major types of tissues that will support the embryo's development. The trophectoderm is the one that connects the fetus to the mother and gives her oxygen and nutrition. The embryo will grow from the primitive endoderm to the yolk sac, where it will receive vitamins and minerals.

There are three types of stem cells that can be derived from the mouse embryo.

The mouse embryo model reported in the new paper is only made of one type of stem cell: the embryonic stem cells. The embryo's body is not treated. One set of developmental signals can be provided by extraembryonic endoderm stem cells. The team drives a third line to become trophoblast stem cells, which give a second set of signals. The team is able to reconstitute the mouse embryo's tissues by starting with only ESCs. The important signaling events between the three tissues are still preserved despite the simplified protocol.

Only the ESCs have the ability to develop into any tissue of the body, and that is the only stem cell type that is pluripotent. The other types of extra-embryonic stem cell are required to do this. There are two extra-embryonic cell types. We end up with three different cell types from the single line.

More information: Kasey Y.C. Lau et al, Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development, Cell Stem Cell (2022). DOI: 10.1016/j.stem.2022.08.013 Journal information: Cell Stem Cell , Nature