The state of the science in culturing totipotent stem cells

A review in the journal Cell Stem Cell by two Jackson Laboratory (JAX) scientists reports on the latest efforts to isolate and culture the elusive populations of stem cells that most closely resemble very early (two-cell stage) totipotent cells.

Small, transient populations of these totipotent cells are found in both mouse and human cultured stem cells. Understanding the workings of the totipotent cell, defined as “a single cell that can give rise to a new organism given appropriate maternal support,” is key to fulfilling the promise of regenerative medicine as well as advancing understanding of the details of mammalian development.

Pluripotent stem cells, from a slightly later stage, can give rise to any specific tissue, but they fail to support more fundamental development such as growing organs for transplantation or building new mouse models. Being able to isolate stable populations of totipotent cells in culture would therefore be highly valuable for research and have potential medical significance.

In the paper, JAX Professor Martin Pera, Ph.D., and Assistant Professor Christopher Baker, Ph.D., note that more refined knowledge of the differences between pluripotent and totipotent stem cells is needed, particularly the molecular regulatory networks that govern cell fate decisions in early mammalian development.

They describe current attempts to isolate the totipotent cells found in stem cell cultures, which involve manipulating gene networks or intercellular signaling pathways. The latter has given rise to what are known as expanded potential stem cells, or EPSCs. They artificially differ from normal two-cell state cells, however, and while possibly useful, their roles in research, such as models for embryo development, will need to be assessed.

“Though many issues remain unresolved,” Pera and Baker write, “the emerging field of totipotent stem cell culture is already helping to illuminate the molecular regulatory networks that govern cell fate decisions in early mammalian development, and is liable to empower our efforts to exploit stem cells in animal biotechnology and medicine in the future.”


Christopher L. Baker, Martin F. Pera. Capturing Totipotent Stem CellsCell Stem Cell. 4 Jan 2018.

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