How signals tell cells what to become: progress towards cell replacement therapy for Diabetes

Dr Gillian Morrison joined the MRC Centre for Regenerative Medicine in 2014 to work on stem cells and Diabetes. More specifically, she is looking at ways to make beta cells from pluripotent stem cells.

Beta cells in the pancreas produce, store and release insulin, the hormone responsible for regulating levels of glucose in the blood. In people with diabetes these beta cells are destroyed (type 1 diabetes) or are unable to produce enough insulin (type 2 diabetes).

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In order to make pancreatic cells in the laboratory, a series of highly controlled steps need to be taken to direct the cell from an unspecialised pluripotent stem cell first to an endoderm cell and then on to a highly specialised beta cell suitable for transplantation.

This process is largely determined by the signals a cell receives from the environment it grows in – we know the identity of these signals but, in most cases, we don’t understand how they instruct cells to become specialised.

Dr Morrison investigated how the first cells along this pathway, endoderm cells, are specialised using cells grown in the laboratory. She uncovered that many different signals interact with each other to ensure the correct cell type is made.

The study was published in EMBO Journal on 16 December 2015.

Dr Gillian Morrison said:

Our works shows how we can accurately instruct a cell what to become by controlling the signals it receives. By studying this signalling process we aim to develop efficient protocols to direct human cells in a dish towards specialised cell types such as beta cells to treat Diabetes.

In addition, the cell signals we are studying here are the same as the ones that go wrong during cancer so by studying how they work normally we gain understanding of what goes wrong in the disease.

Our next step will be to generate large numbers of functional human pancreatic cells in the laboratory. To do this we will try to copy the development of these cells in the human body and also try some new and exciting synthetic biology approaches.

The work was done at the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge and the MRC Centre for Regenerative Medicine, University of Edinburgh. It was funded by the Juvenile Diabetes Research Foundation International, the European Commission FP7 project BetaCellTherapy, further supported by the Wellcome Trust, Medical Research Council and the University of Edinburgh.

Notes to editors

Publication details

Morrison G, Scognamiglio R, Trumpp A, Smith A. 2015. Convergence of cMyc and β-catenin on Tcf7l1 enables endoderm specification. EMBO Journal. embj.201592116. DOI 10.15252/embj.201592116. Published online 16 December 2015.