Publication

Epithelial stem cells and mechanical signal transduction

Vincent Bernard Cattin
2008
Thèse EPFL
Résumé

Hair follicles are cutaneous structures characteristic of mammals. These sensitive organs cycle and contain multipotent epithelial stem cells which are implicated in hair growth and hair cycle. A single whisker follicle of the rat hosts up to 1500 stem cells, many more than necessary to regenerate the entire follicle throughout the animal's life. These cells are preferentially located in the most innervated region of the hair follicle. We hypothesised that stem cells might have an additional function aside from tissue renewal: stem cells may be involved in the mechanical signal transduction between hair follicle and afferent nervous system. This supplemental role may either take place through the interaction of the multipotent epithelial stem cells with nerve endings, or through neuroepithelial Merkel cells acting as intermediates. Merkel cells are located in the basal layer of the whisker follicle outer root sheath (ORS) and share a close relationship with their neighbouring nerve endings. These cells specifically express the transcription factor Math1 and their function is poorly understood. We demonstrate here by clonal analysis and transplantation assays that Merkel cells are not derived from epithelial stem cells. In addition, Math1-expressing cells isolated from the epidermis are unable to form colonies and to participate in the generation epidermal lineages when transplanted, failing to show stemness properties. Furthermore, when cultured in conditions that favour the growth of neurospheres, they are unable to proliferate, revealing a different behaviour than that of skin-derived neural crest cells. We also demonstrate that multipotent epithelial stem cells express several proteins implicated in glutamate neurotransmission, as well as other molecules usually found in the nervous system. The expression of NMDAR and AMPAR subunits, as well as their scaffolding proteins and neurotransmitter vesicular transport-implicated proteins are uncovered for the first time in the multipotent epithelial stem cells from the bulge. Our results support the mechanical signal transduction hypothesis and confirm the increasingly important role of the recently described neural-like structures of the skin. This work paves the way for a better comprehension of multipotent epithelial stem cell behaviour and stem cell-related pathologies.

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Concepts associés (35)
Cellule souche
vignette|Cellules souches embryonnaires de souris en culture. En biologie cellulaire, une cellule souche est une cellule indifférenciée capable, à la fois, de générer des cellules spécialisées par différenciation cellulaire et de se maintenir dans l'organisme par division symétrique ou division asymétrique. Les cellules souches sont présentes chez tous les êtres vivants multicellulaires. Elles jouent un rôle central dans le développement des organismes ainsi que dans le maintien de leur intégrité au cours de la vie.
Stem-cell niche
Stem-cell niche refers to a microenvironment, within the specific anatomic location where stem cells are found, which interacts with stem cells to regulate cell fate. The word 'niche' can be in reference to the in vivo or in vitro stem-cell microenvironment. During embryonic development, various niche factors act on embryonic stem cells to alter gene expression, and induce their proliferation or differentiation for the development of the fetus.
Cellules souches cancéreuses
Les cellules souches cancéreuses (CSCs) sont des cellules cancéreuses (présentes dans les tumeurs dites « solides » ou les cancers hématologiques) qui possèdent des caractéristiques associées aux cellules souches normales, notamment la capacité de donner naissance aux différentes populations de cellules présentes dans une tumeur particulière. Les CSCs sont donc tumorigènes (formant des tumeurs), peut-être à la différence d'autres cellules cancéreuses non tumorigènes.
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