In a groundbreaking achievement, Israeli researchers have transformed rodent skin cells into the three major stem-cell types that comprise early-stage embryos.
Their main goal is to provide a “test tube embryo” as a new way to model and study embryonic defects and placental dysfunctions using lab mice.
In the future, this breakthrough possibly could provide a path toward creating whole human embryos from human skin cells, without the need for sperm or eggs.
Reporting in the journal Cell Stem Cell, Hebrew University of Jerusalem developmental biology and cancer researcher Yossi Buganim and his team explain that they discovered a set of five genes capable of transforming rodent skin cells into all three of the cell types that comprise the early embryo: the embryo, the placenta and the extraembryonic tissues, such as the umbilical cord. These transformations take about one month.
Back in 2006, Japanese researchers discovered that skin cells could be “reprogrammed” into early embryonic cells (“induced plutipotent stem cells”) essentially identical to their natural counterparts. These cells can develop into all fetal cell types, but not into extra-embryonic tissues.
The Hebrew University team used new technology to scrutinize the molecular forces that govern cell fate decisions for skin-cell reprogramming and the natural process of embryonic development.
For example, the researchers observed that the Eomes gene influences placental stem-cell identity and placental development, while the Esrrb gene orchestrates fetal stem-cell development.
To uncover the molecular mechanisms activated during the formation of these various cell types, the researchers analyzed changes to the genome structure and function inside the skin cells when the five genes were introduced.
They discovered that during the first stage, skin cells lose their cellular identity and then slowly acquire a new identity of one of the three early embryonic cell types, and that this process is governed by the levels of two of the five inserted genes.
Recently, attempts have been made to develop an entire mouse embryo without using sperm or egg cells. These attempts used the three early cell types isolated directly from a live, developing embryo.
In contrast, HU’s study is the first attempt to create all three main cell lineages at once from skin cells. These findings mean there may be no need to “sacrifice” a live mouse embryo to create a test-tube embryo for research purposes.
Buganim’s team includes Oren Ram from the university’s Institute of Life Sciences and Prof. Tommy Kaplan from its School of Computer Science and Engineering, as well as doctoral students Hani Benchetrit and Mohammad Jaber.
The study received funding from the Israel Science Foundation, European Research Council, Howard Hughes Medical Institute and I-CORE Israeli Centers of Research Excellence.