A new type of stem cell offers greater development potential

Stem cells have been used extensively for research into development and disease, and have a wide variety of potential applications including the screening of new pharmaceuticals, as tools to study the development of complex organisms, as model systems for identifying the cause of birth defects, and as regenerative therapeutics. With their ability for self-renewal through cell division, and their capacity to be induced into specific cell types, they are an extremely powerful tool.

While embryonic stem cells (ES) are derived from the embryo, adult stem cells are found amongst differentiated cells in a wide range of tissues, where they perform essential maintenance and repair functions. Induced pluripotent stem cells (iPSC) are derived from adult stem cells, and are genetically modified to cause them to behave as ES. While both ES and iPSC are pluripotent, neither is capable of forming every possible kind of cell since each type is precluded from the development of certain cell lineages.

In a Nature article published in October 2017, a group of researchers described the creation of a new type of murine stem cell line, Expanded Potential Stem Cells (EPSC), offering greater capacity for development than either ES or iPSC. This cell line was established from individual eight-cell blastomeres (the collection of cells which results from cleavage of a fertilised egg), and also by direct conversion of murine ES and iPSC.

To generate EPSC from blastomeres, Yang et al used a cocktail of inhibitors to block blastomere differentiation by targeting Mitogen-Activated Protein Kinases (MAPKs), Src and Wnt / Hippo / Tankyrase1/2; they referred to the media containing these inhibitors as Expanded Potential Stem Cell Medium (EPSCM). The rationale for selecting these targets was that previous studies had shown them to play key roles in signalling pathways affecting trophectoderm / inner cell mass segregation, therefore pathway modulation was postulated to halt blastomere differentiation and enable cell lines to be derived.

The established stem cell lines were shown to express pluripotency genes similar to those of conventional ES cells and, following injection into a morula (a collection of around thirty cells), contributed both to the inner cell mass and to the trophectoderm. To put this into context, when re-introduced to the blastocyst, murine ES derived from the epiblast (the outermost layer of an embryo before it differentiates into ectoderm, mesoderm and endoderm) can contribute to the somatic cell lineages and germline, but are excluded from the extra-embryonic tissues that are derived from the trophectoderm.

Murine ES and iPSC were converted to EPSC by culturing them in the specialised media, EPSCM, however when they were returned to their original growth media their expanded potential was lost and they reverted to ES cells.

EPSC have much greater development potential than ES or iPSC since they are the very earliest cell type. Although this particular study was performed in mouse, the methods which were used pave the way for similar work to be carried out with human cells, and afford huge opportunities for human regenerative medicine.