How can we change stem cells into brain cells?

Lead Investigator: Dr Virginie Sottile

Institution: University of Nottingham

Grant type: Project

Grant amount: £99,888

Start date: 1/10/12 

Completion date: 28/02/15

Scientific Title: Regulation of the pro-neural gene Sox1 to regulate stem cell potential.

What was the project, and what did the researchers do?

Adult stem cells are found in nearly all tissues in the body and are known as 'immature' or 'precursor' cells. They are early stage cells that then develop into different mature cells. For example, stem cells found in the brain can mature into various brain-related cells such as neurons or astrocytes in response to specific signals. As symptoms of dementia are often caused by the death of cells in the brain, stem cells may be able to help by creating new cells.

However the use of brain stem cells in research present a difficulty as they are not easy to access. Researchers are therefore looking for other sources of adult stem cells. Stem cells found in the bone marrow are more accessible and are already used to treat different conditions such as repairing bone and cartilage. Unfortunately bone marrow stem cells can't currently be used as a dementia treatment because they don't naturally mature into brain cells. 

This project set out to identify factors that promote the formation and development of normal brain cells. This occurs when a particular gene found in the stem cell, known as Sox1, is activated. Finding out what mechanisms activate Sox1 mean the researchers could artificially activate the gene in the bone marrow stem cells, causing them to become brain cells. If this technique is successful, these cells could have the potential to be used in the treatment of dementia. 

To find what factors control the activation of this gene, the researchers compared the DNA of brain stem cells to the DNA of bone marrow stem cells and determine the main differences between the two. 

What were the key results, and how will this help in the fight against dementia?

Genes are often surrounded by other types of DNA that can sometimes affect the gene's function. The researchers found that the DNA around the Sox1 gene in the bone marrow cells was noticeably different to the DNA surrounding the gene in brain cells. This suggested that a mechanism called epigenetics was involved. 

Epigenetics are another layer of information that can also affect gene function. Epigenetic modifications are chemical tags that can be added to DNA and have the ability to influence a gene's function without altering its makeup. These changes can be also influenced by external factors such as the environment. In this case, the epigenetic modifications seemed to be giving brain cells the ability to activate Sox1, whilst preventing bone marrow cells from doing the same. 

When comparing the DNA, researchers also identified another set of genes that differ between the brain and bone marrow cells. These genes also seemed to be involved in activating Sox1 and researchers carried out experiments that further uncovered the role of these genes in brain cell development. 

In addition, researchers discovered a new type of gene sequence not previously seen in brain stem cells. They have begun to investigate what role it may play but more research is needed to fully understand its significance. 

These results highlight the roles of specific genes that are involved in the production of new brain cells. The findings help us better understand the processes in the brain and could potentially help us to develop treatments for dementia in the future. 

What happened next? Future work and additional grants

The researchers are continuing this work and have applied for grants to further explore this area. They are also applying for funding to further investigate the role of the newly discovered gene sequence. This line of investigation is currently taking place in collaboration with a PhD student in the research group funded by the University of Nottingham. This will help researchers to collect more evidence and prepare published work on this project. 

How were people told about the results? Conferences and Publications

Papers (soon to be published)

One publication is presenting the results of the transcriptional regulation analysis and its experimental testing.

The second paper will describe original dataset demonstrating the detection of the overlapping transcript.

Conference presentations 

Bioinformatics project presentation, University of Leicester, November 2013

Alzheimer's Society Research conference, Nottingham, July 2014

Conference poster presentations

Alzheimer's Society Research conference, Leeds, October 2012