Stem cells from the thymus reprogrammed to become skin stem cells

Embargoed until (GMT): 
19 Aug 2010 - 9:00am UTC

New research published on 19 August 2010 in Nature points to the possibility of direct reprogramming of one stem cell type to another without the need for genetic modification and raises prospects for regenerating organs.

The study shows that stem cells from the thymus, a specialized organ of the immune system, can function as hair follicle stem cells and contribute to the long-term maintenance of the skin, a completely different organ.

In this study a group of cells called thymic epithelial cells (TECs) were isolated from the rat, cultured in the lab under conditions used to grow skin stem cells and tested for function and for genetic markers of thymus and skin cell types. They were then transplanted into developing skin.

On transplantation, the cells displayed different genetic markers – those of hair follicle stem cells. They were also able to contribute to maintenance of both skin and hair for more than a year - outperforming bona fide hair follicle stem cells, which can only renew the skin for 3 weeks or after injury.

These experiments show that cues from the local microenvironment – in this case skin - can ‘reprogramme’ stem cells to contribute to tissues they are not normally able to generate. They also raise new questions about relationships between stem cells from different tissues within the body.

"These cells change because of the environment they come into contact with, the skin" comments Professor Yann Barrandon, Joint Chair of Stem Cell Dynamics EPFL/CHUV-UNIL, who led the study. "In theory this operation could be recreated with other organs as well."

When the body plan of an animal is formed, embryos develop into three cellular (germ) layers - ectoderm, endoderm and mesoderm – and from these layers into the organs and tissues of the body. Ectoderm becomes skin and some nerves, endoderm becomes the gut and organs such as the liver, pancreas and thymus, and mesoderm becomes muscle and blood. Before now we believed that germ layer boundaries could not be crossed – that cells originating in one germ layer could not develop into cells associated with one of the others.

This new research shows that cells from the thymus (endoderm origin) can turn in to skin stem cells (ectoderm origin) and suggests germ layer boundaries are less absolute than previously thought.

Dr Clare Blackburn, thymus specialist at the University of Edinburgh's MRC Centre for Regenerative Medicine and an author on this paper, comments: “It’s not just that a latent capacity is triggered or uncovered when these stem cells come in to contact with skin. They really change track – expressing different genes and becoming more potent. It will be interesting to see whether microenvironments other than skin have a similar effect.”

This work is the result of a long-running collaboration between scientists in Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland and the MRC Centre for Regenerative Medicine at the University of Edinburgh in the UK begun as part of EU Sixth Framework project EuroStemCell and continued under the FP7 projects EuroSyStem and OptiStem.

Notes for editors
  1. The paper ‘Microenvironmental Reprogramming of Thymic Epithelial Cells to Skin Multipotent Stem Cells’ by Bonfanti et al will be published in Nature on 19 August 2010 and is available from Yann Barrandon (yann [dot] barrandon [at] epfl [dot] ch) on request.
  2. This work was funded by the European Commission through the EuroStemCell, OptiStem and EuroSyStem projects, and by the Swiss National Science Foundation, the Juvenile Diabetes Research Foundation and Leukaemia & Lymphoma Research.
  3. EuroStemCell - the European Consortium for Stem Cell Research - was an Integrated Project funded under the EU's Sixth Framework Programme. It combined the expertise of more than 100 researchers across 27 research groups to build the scientific foundations required to take stem cell technology to the clinic. www.eurostemcell.org
  4. EuroSyStem is an EC funded partnership of 25 research groups in eight countries. Its focus is on answering questions in fundamental stem cell biology. Its partners combine computational and biological expertise to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. www.eurosystemproject.eu
  5. Optistem is a large-scale integrated project funded by the European Commission to test new stem cell-based approaches to treating degenerative diseases of skeletal muscle, and diseased or damaged epithelial tissues such as skin or the surface of the eye. www.optistem.org
  6. The Swiss National Science Foundation (SNSF) is the most important Swiss agency promoting scientific research. It supports, as mandated by the Swiss Federal government, all disciplines, from philosophy and biology to the nanosciences and medicine. www.snf.ch
  7. The Juvenile Diabetes Research Foundation exists to find the cure for type 1 diabetes and its complications, and is the world’s leading charitable funder of type 1 diabetes research. At a global level JDRF volunteers and staff have been responsible for raising over £800 million to support type 1 diabetes research since the charity’s inception. www.jdrf.org.uk
  8. Leukaemia & Lymphoma Research is the only UK charity solely dedicated to research into blood cancers, including leukaemia, lymphoma and myeloma. These cancers are diagnosed in around 28,500 children, teenagers and adults in the UK every year. Leukaemia & Lymphoma Research was previously known as Leukaemia Research and has changed its name to raise awareness of its longstanding commitment to research into all the blood cancers - not just leukaemia. Further information, including patient information booklets, is available from www.llresearch.org.uk or on 020 7405 0101.
  9. The MRC Centre for Regenerative Medicine is based at the University of Edinburgh and brings together world leading basic stem cell research with established clinical excellence to deliver a "bench-to-bedside" approach aimed at developing new treatments for major diseases including cancer, heart disease, diabetes, multiple sclerosis, Parkinson's disease, and liver failure. www.crm.ed.ac.uk
  10. EPFL is the research home of the beginning of the modern computer mouse, of the ambitious Blue Brain Project, and of innovative ideas towards sustainable development. Offering tuition at all levels from undergraduate to PhD, it is one of the world’s fastest growing campuses. It is currently ranked alongside Cambridge as the top university in Europe in the category of engineering, technology and computer sciences according to the Shanghai Academic Ranking of World Universities (ARWU). www.epfl.ch
  11. CHUV is the Lausanne University Hospital. www.chuv.ch
Publication details

This study was published in Nature on 19 August 2010:
Microenvironmental Reprogramming of Thymic Epithelial Cells to Skin Multipotent Stem Cells. Paola Bonfanti, Stéphanie Claudinot, Alessandro W. Amici, Alison Farley, C. Clare Blackburn and Yann Barrandon.