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In an innovative feat, Israeli researchers have transformed rodent skin cells into three main types of stem cells that include 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 laboratory mice.
In the future, this breakthrough could create whole human embryos from human skin cells without the need for sperm or eggs.
In the Cell Stem Cell Journal of Developmental Biology and Cancer, The Hebrew University of Jerusalem, Yossi Buganim and his team explain that they have discovered a set of five genes capable of transforming skin cells rodent into three types of cells constituting the early embryo: the embryo, placenta and extraembryonic tissues, such as the umbilical cord. These transformations take about a month.
Professor Yossi Buganim. Photo by Shai Herman
In 2006, Japanese researchers had discovered that skin cells could be "reprogrammed" into early embryonic cells ("induced progeny cells") essentially identical to their natural counterparts. These cells can grow in all types of fetal cells, but not in extraembryonic tissues.
The Hebrew University team used new technology to examine the molecular forces that govern cell fate decisions for reprogramming skin cells and the natural process of embryonic development.
For example, researchers observed that the Eomes gene influenced the identity of placenta stem cells and placental development, while the Esrrb gene orchestrated the development of fetal stem cells.
To discover the molecular mechanisms activated during the formation of these different types of cells, researchers badyzed changes in the structure of the genome and their functioning in skin cells during the introduction of the five genes.
They discovered that during the first stage, the skin cells lose their cellular identity and then slowly acquire the new identity of one of three early embryonic cell types. This process is governed by the levels of two of the five genes inserted.
Recently, attempts have been made to develop an entire mouse embryo without the use of sperm or egg cells. These attempts used the three early cell types isolated directly from a living developing embryo.
In contrast, the HU study is the first attempt to simultaneously create the three major cell lines from cutaneous cells. These findings mean that it may not be necessary to "sacrifice" a live mouse embryo to create a test tube embryo for research purposes.
The Buganim team includes Oren Ram from the Institute of Life Sciences of the University and Prof. Tommy Kaplan from his computer and engineering school, as well as PhD students Hani Benchetrit and Mohammad Jaber.
The study received funding from the Israel Foundation for Science, the European Research Council, the Howard Hughes Medical Institute and the Israeli research centers of excellence I-CORE.
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