Abstract
The formation of hair follicles, a landmark of mammals, requires complex mesenchymal–epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo. Here, we demonstrate that epithelial stem cells of non-skin origin (e.g. that of cornea, oesophagus, vagina, bladder, prostate) that express the transcription factor Tp63, a master gene for the development of epidermis and its appendages, can respond to skin morphogenetic signals. When exposed to a newborn skin microenvironment, these cells express hair-follicle lineage markers and contribute to hair follicles, sebaceous glands and/or epidermis renewal. Our results demonstrate that lineage restriction is not immutable and support the notion that all Tp63-expressing epithelial stem cells, independently of their embryonic origin, have latent skin competence explaining why aberrant hair follicles or sebaceous glands are sometimes observed in non-skin tissues (e.g. in cornea, vagina or thymus).
Highlights
The formation of hair follicles, a landmark of mammals, requires complex mesenchymal– epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo
We have demonstrated that the thymus of the rat contains clonogenic tumor protein 63 (Tp63)-expressing epithelial cells of endodermal origin that can behave as bona fide multipotent stem cells of hairy skin when transplanted into a developing skin microenvironment[18]
Our experiments demonstrate that Tp63-expressing epithelial stem cells of non-hairy tissues and of different embryonic origin can cross lineage boundaries when exposed to a different microenvironment
Summary
The formation of hair follicles, a landmark of mammals, requires complex mesenchymal– epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo. We demonstrate that epithelial stem cells of non-skin origin (e.g. that of cornea, oesophagus, vagina, bladder, prostate) that express the transcription factor Tp63, a master gene for the development of epidermis and its appendages, can respond to skin morphogenetic signals. We have demonstrated that the thymus of the rat contains clonogenic Tp63-expressing epithelial cells of endodermal origin that can behave as bona fide multipotent stem cells of hairy skin when transplanted into a developing skin microenvironment[18] These observations together with the fact that hair follicles and dermoid cysts are observed in a variety of nonskin tissues in adult mammals (cornea, oral cavity, esophagus, thymus) (Supplementary Table 2) strongly suggest that the ability to respond to skin morphogenetic signals is not restricted to embryonic epidermal stem cells, a notion supported by the generation of de novo hair in the adult mouse after wounding[19]. Some epithelial cells (bladder, prostate, thymus) necessitate a passage in cell culture to respond to a skin microenvironment, supporting the notion that tissue stem/progenitor cells may broaden potency in response to cell culture, a phenomenon thought to be associated with stem cell plasticity and reprogramming[22,23]
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