Signalling molecule Wnt biases the earliest fate choices of pluripotent cells

6 March 2014

During early development, cells in the embryo are able to form all specialised cell types, but because each cell happens to exist in a particular area of the embryo, these so-called pluripotent cells don't form all cell types, but only the ones typical of the position they find themselves in.

petri dish of EpiSCs
Image shows a petri dish of EpiSCs and how this apparently homogeneous population of cells is not homogeneous at all. Different cells express a primitive streak marker (T-dsRed, red), E-cadherin (purple) and N-cadherin (green).

CRM researchers, led by Dr Val Wilson, wondered if the pluripotent yet regionalised cells in the embryo are intrinsically biased towards making the cell types they eventually make, or if they are guided

entirely by signals from their own local area.

The team used pluripotent cells similar to the embryo at this stage, known as Epiblast Stem Cells (EpiSCs), to answer this question, and confirmed their results by re-introducing the cells to early mouse embryos.

Their study, published in the scientific journal Development, showed that at least some of the EpiSCs have intrinsic biases, which do not exclude them from making all cell types, but just make it less likely that they will make inappropriate cell types. The researchers found two types of biased cells: one that prefers to make nervous system and the other that prefers to make gut and heart muscle.

The team also discovered that increasing the levels of a particular signalling molecule known as Wnt commits biased cells to making the specialised cell types of the nervous system, gut, and heart muscle, as well as muscles associated with the skeleton. This latter cell type (known as the neuromesodermal progenitor) was first identified in the early embryo itself.

Dr Val Wilson said:

“This research is important because it shows how closely a cultured cell type, the Epiblast Stem Cell, resembles cells in the embryo, so we can examine in a culture dish how cells make early choices that will eventually determine whether they will be part of the brain, gut or skeleton and spinal cord."

The study, published online in Development on Wednesday 5 March, was supported by the Association for International Cancer Research (AICR) and the Medical Research Council (MRC).

A winning video showcasing previous work done by Yali Huang, PhD student in the Early Embryo Development Group: