Thymic cells have potential to form multipotent skin cells
MedWire News: Thymic epithelial cells (TECs) taken from the rat thymus can irreversibly adopt the fate of multipotent hair follicle stem cells when exposed to an inductive skin microenvironment, study results show.
Despite the different embryologic origins of thymus and skin (endodermal and ectodermal, respectively), the thymic cells adopted robust changes in gene expression.
"Not only could these findings create new opportunities in the field of organ transplantation and regeneration, for severe burn victims for example, but they also call into question standard biological models by showing that it is possible to create tissues from cells with different embryonic origins," say Yann Barrandon (Ecole Polytechnique Fédérale de Lausanne [EPFL], Switzerland) and colleagues.
The thymus is a specialized organ of the immune system, whose primary function is the production of T-lymphocytes.
Thymic epithelial cells play an essential support role in this process by facilitating generation of self-tolerant thymocytes through expression of the autoimmune regulator Aire5.
To investigate mechanisms involved in the specification and maintenance of TECs, the researches performed a series of in vitro and in vivo experiments in a rat model.
Firstly, TECs were isolated from embryonic, post-natal or adult thymus and cultured in vitro. These TECs maintained the ability to contribute to thymic morphogenesis when transplanted back into thymus tissue aggregates.
The researchers then tested the capacity of clonogenic TECs to participate in the formation of hair follicles and epidermis in a short-term reconstitution assay in vitro.
After 2-3 weeks, TECs were detected in all epidermal and hair follicle layers, clearly indicating that clonogenic TECs were able to generate skin lineages in response to skin morphogenetic signals.
To investigate if TECs could participate in long-term hair follicle renewal, the researchers transplanted cells to the skin of a rat. They then harvested a skin graft and isolated and cultured TECs, and re-transplanted them into the rat skin.
The TECs were able to renew the epidermis and incorporate into hair follicles that cycled for more than 100 days - in contrast to bona fide hair follicle, multipotent stem cells that can only generate epidermis for 3 weeks.
"TECs may have an inherent capability to form skin, as revealed by our assay, as they naturally express markers of skin differentiation in vivo," Barrandon et al conclude in the journal Nature.
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By Andrew Czyzewski