Stem cell biology research group

The stem cell biology research group is based within the Basic Sciences research theme at Manchester.

Staff

This group studies embryonic stem (ES) cell pluripotency, with particular focus on the role of adhesion molecules and their relation to molecular mechanisms of development and tumorigenesis. Investigations have shown that the cell surface protein E-cadherin regulates mouse ES cell pluripotency via phosphorylation of STAT3. E-cadherin expression has also been found to inhibit plasma membrane localisation of the pro- migratory 5T4 oncofoetal antigen in ES cells.

The group has also demonstrated that ES cell differentiation is associated with an epithelial- mesenchymal transition (EMT) event that exhibits striking similarities to tumour cell metastasis. It has further shown that loss of N-cadherin or 5T4 in ES cells results in decreased motility of the cells during EMT.

Recently, it discovered that E-cadherin functions in mouse (m)ES cells to regulate LIF/BMP-dependent self-renewal. Abrogation of E-cadherin in mES cells results in maintenance of pluripotency via Activin/Nodal, while self-renewal is enhanced via Fgf2 signalling. Therefore, E-cadherin functions to maintain both epithelial integrity and pluripotent signalling pathways in ES cells. We have further demonstrated that N-cadherin can function in a similar manner to E-cadherin in mES cells.

In addition, the group is researching new methods for the culture and differentiation of ES cells in bioreactors. The rationale for these studies is that a current bottleneck to the clinical applications of these cells remains the limited cell numbers achieved using conventional culture techniques.

It has been demonstrated that mES cells cultured in shake flasks over 15 days maintain pluripotency and can differentiate to the three germ layers. In addition, we have developed a technology for the rapid differentiation of human ES cells to neural progenitor cells. This method may help in the understanding of neural development as well as being a useful tool for drug testing applications.

Current postgraduate research students

• Zahra Youssef Abdalla
• Natalie Miazga
• Joe Segal
• Fabiana Louise
• Anoum Al-Mudhani
• Hassan Kaabi
• Aseel Sharaireh