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New ‘expanded potential stem cells’ could shed light on developmental disorders

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For the first time, researchers have created expanded potential stem cells (EPSCs) in mice that, they report, have a greater potential for development than current stem cell lines. These stem cells have the features of the very first cells in the developing embryo and can develop into any type of cell.

The methods used could also help produce similar stem cell lines from human and other mammalian species, including those such as pigs or cows, where embryonic stem cell lines are still not available.

The researchers, from the Wellcome Trust Sanger Institute (Cambridgeshire, UK) and Stanford University, (California, US) also believe that their study (published October 11 in Nature) could have implications for human regenerative medicine and for understanding miscarriage and developmental disorders.

Existing stem cell lines are already extremely useful for research into development, disease and treatments. However, the two currently available types of stem cell lines — embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) — have certain limitations, including they cannot form every type of cell since they are already excluded from developing certain cell lineages.

To discover new stem cells for use in research and regenerative medicine, the researchers created a way of culturing cells from the earliest stage of development, when the fertilized egg has only divided into four or eight cells that are still considered to retain some totipotency — the ability to produce all cell types. Their hypothesis was that these cells should be less programmed than ESCs, which are taken from the around-100-cell stage of development (called a blastocyst). They grew these early cells in a special growth condition that inhibited key development signals and pathways.

The scientists discovered that their new cultured cells — the EPSCs — kept the desired development characteristics of the earliest cells. They were also able to reprogram mouse ESCs and iPSCs in the new condition and create EPSCs from these cells, turning back the development clock to the very earliest cell type.

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DOI: 10.1038/nature24052