Totipotent or not totipotent – the identity issues of a 2-cell-like cell

Who am I? Probably, everyone has asked this question to oneself or has gotten identical issues, at least once per lifetime. Identity is defined as the distinguishing character or personality of an individual (Merriam Webster Dictionary). Our body cells also can have identity issues, but quite different to ours. In their recent review article, Marion Genet and Prof. Maria-Elena Torres-Padilla from the Institute for Epigenetics and Stem Cells of the Helmholtz Zentrum München explain the identity issues of 2-cell-like cells and discuss whether they can or cannot be used as an in vitro model for totipotency.


The use of cell culture-based (in vitro) tissue cell models builds the fundament of biomedical research. Such in vitro systems improve our understanding for basic cell biology, tissue morphology, cellular plasticity and disease mechanisms. Moreover, they are used as a tool to study drug development and to advance tissue engineering and stem cell therapies.

For example, the in vitro models for pluripotency*, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have led to a better understanding of pluripotency, early embryonic development and cell differentiation, as well as to groundbreaking discoveries in regenerative medicine. However, in terms of cellular potency – the ability of a cell to differentiate into other cell types - a totipotent cell is much more powerful than a pluripotent cell because it can give rise to a full organism by itself. Thus, understanding how these totipotent cells function is very important for regenerative medicine and disease. The recent discovery of 2-cell-like cells in a mouse ESCs culture provided the unique possibility to establish an in vitro model system for totipotency because they resemble the totipotent 2-cell-stage embryo of mice. 2-cell-like cells have emerged as a trackable system to understand, mechanistically, some of the molecular features of the cells in the early embryos, which are extremely plastic. Therefore, using 2-cell-like cells to understand cellular plasticity, origin of stem cells and their potential is a great opportunity.

In their review article published recently in Development, Marion Genet and Prof. Maria-Elena put together the available literature to provide the community an up-to-date reference guide of the molecular characteristics of 2-cell-like cells and discuss whether they can or cannot be declared as truly totipotent.

To read the article go here.

Further information:

* Pluripotency: Ability of a cell to form all the germ layers (endoderm, mesoderm, ectoderm). However, a pluripotent cell cannot differentiate into extra-embryonic tissues, such as the placenta, and thus, is not able to give rise to full organism on its own.