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 epithelia. 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.
Bonfanti
Paola
P
Laboratory of Stem Cell Dynamics, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Claudinot
Stéphanie
S
Amici
Alessandro W
AW
Farley
Alison
A
Blackburn
C Clare
CC
Barrandon
Yann
Y
D000818:Animals; D018929:Cell Culture Techniques; D054337:Cell Dedifferentiation; D019070:Cell Lineage / Q000502:physiology; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000166:cytology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008297:Male; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000166:cytology* / Q000196:embryology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology; D014157:Transcription Factors / Q000378:metabolism; D000096927:AIRE Protein
D000949:Histocompatibility Antigens Class II; D014157:Transcription Factors; D000096927:AIRE Protein