Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells.

Details

Serval ID
serval:BIB_858D0051ED4C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells.
Journal
Nature
Author(s)
Bonfanti Paola, Claudinot Stéphanie, Amici Alessandro W., Farley Alison, Blackburn C.Clare, Barrandon Yann
ISSN
1476-4687[electronic], 0028-0836[linking]
Publication state
Published
Issued date
2010
Volume
466
Number
7309
Pages
978-982
Language
english
Abstract
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.
Keywords
hair-follicles, progenitor cells, clonal analysis, tolerance, identification, organogenesis, regeneration, keratinocyte, generation, aire
Pubmed
Web of science
Create date
01/09/2010 13:17
Last modification date
20/08/2019 14:44
Usage data