Novel interaction in cell reprogramming discovered

ß-catenin (represented by GFP signal in immunofluorescence experiment) is heterogeneously expressed in mouse embryonic stem cells

The study is published in Cell Reports and was a collaborative project conducted by Dr Lucia Marucci in the Department of Engineering Mathematics at the University of Bristol, Elisa Pedone at the Centre for Genomic Regulation (CRG), Barcelona and led by Maria Pia Cosma at the CRG.

Nanog, a known key regulator of pluripotency, and ß-catenin, a main regulator of both pluripotency and differentiation, are key regulators of ESC pluripotency and cell reprogramming. Pluripotency is one of the main features of stem cells: they have the capability of each becoming specialised cell type. Researchers have shown that the two proteins regulate pluripotency and reprogramming together, due to an indirect activation of Nanog on ß-catenin.

The study found this novel interaction is fundamental in cell reprogramming. Reprogramming experiments were performed with two techniques: cell fusion mediated reprogramming and the generation of induced pluripotent stem cells (iPSCs).

Dr Lucia Marucci, Lecturer in Engineering Mathematics, said: "Importantly, the novel interaction between Nanog and ß-catenin controls time variations of ß-catenin in mouse ESCs. We developed a mathematical model that showed the dynamics of the protein were stochastic.

"The results of our work are the basis for a deeper knowledge of biological interactions and dynamics of mouse ESCs that could be used in the future to optimise the pluripotency of mouse ESCs and the reprogramming of cells back to pluripotency."

Embryonic stem cells (ESCs) are unspecialised stem cells derived from the embryo. They are characterised by the ability of propagating indefinitely, under self-renewal, and are easy at differentiating in every specialised cell type (pluripotency). These characteristics make embryonic stem cells a great tool for scientists to study the development of living organisms.

Recently it has been discovered that it is possible to reprogram specialised cells back to a pluripotent, stem-like state. At present, it is not yet possible to directly use these cells for medical application, mainly due to a scarce knowledge researchers have about the basic biological processes behind.

ß-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to Pluripotency, Lucia Marucci, Elisa Pedone, Umberto Di Vicino, Blanca Sanuy-Escribano, Mark Isalan, Maria Pia Cosma, Cell Reports, published online 4 September 2014.

Source: Bristol University