Reprogrammed Thymus Stem Cells Could Help Tissue Regeneration

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Researchers, who used rat models, grew stem cells from the thymus – an organ important for our immune systems – in the laboratory using conditions for growing hair follicle skin stem cells.

When the cells were transplanted into developing skin, they were able to maintain skin and hair for more than a year. The transplanted follicles outperformed naturally-produced hair follicle stem cells, which are only able to heal and repair skin for three weeks. Once they were transplanted, the genetic markers of the cells changed to be more similar to those of hair follicle stem cells. The research, published in the journal Nature, shows that triggers from the surrounding environment – in this case from the skin – can reprogramme stem cells to become tissues they are not normally able to generate.

Professor Yann Barrandon, Joint Chair of Stem Cell Dynamics at the Ecole Polytechnique Fédérale de Lausanne, Université de Lausanne and Centre Hospitalier Universitaire Vaudois, who led the study, said: “These cells change because of the environment they come into contact with, the skin. In theory this operation could be recreated with other organs as well.”

When an animal develops, embryos form three cellular or germ layers – ectoderm, endoderm and mesoderm – which then go on to form the body’s organs and tissues.

Ectoderm becomes skin and nerves, endoderm becomes the gut and organs such as the liver, pancreas and thymus, and mesoderm becomes muscle, bones and blood.

Until now it was 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 latest research shows that thymus cells, originating from the endoderm, can turn in to skin stem cells, which originate from the ectoderm origin. This suggests germ layer boundaries are less absolute than previously thought.

Nature – Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells

The thymus develops from the third pharyngeal pouch of the anterior gut and provides the necessary environment for thymopoiesis (the process by which thymocytes differentiate into mature T lymphocytes) and the establishment and maintenance of self-tolerance. It contains thymic epithelial cells (TECs) that form a complex three-dimensional network organized in cortical and medullary compartments, the organization of which is notably different from simple or stratified epithelia4. TECs have an essential role in the generation of self-tolerant thymocytes through expression of the autoimmune regulator Aire but the mechanisms involved in the specification and maintenance of TECs remain unclear. Despite the different embryological origins of thymus and skin (endodermal and ectodermal, respectively), some cells of the thymic medulla express stratified-epithelium markers interpreted as promiscuous gene expression. Here we show that the thymus of the rat contains a population of clonogenic TECs that can be extensively cultured while conserving the capacity to integrate in a thymic epithelial network and to express major histocompatibility complex class II (MHC II) molecules and Aire. These cells can irreversibly adopt the fate of hair follicle multipotent stem cells when exposed to an inductive skin microenvironment; this change in fate is correlated with robust changes in gene expression. Hence, microenvironmental cues are sufficient here to re-direct epithelial cell fate, allowing crossing of primitive germ layer boundaries and an increase in potency