Actin filament dynamics impacts keratinocyte stem cell maintenance.

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Version: author
Serval ID
serval:BIB_3C8B4DF829BE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Actin filament dynamics impacts keratinocyte stem cell maintenance.
Journal
EMBO Molecular Medicine
Author(s)
Nanba D., Toki F., Matsushita N., Matsushita S., Higashiyama S., Barrandon Y.
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Publication state
Published
Issued date
2013
Volume
5
Number
4
Pages
640-653
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish. PDF type: Research article
Abstract
Cultured human epidermal keratinocyte stem cells (holoclones) are crucial for regenerative medicine for burns and genetic disorders. In serial culture, holoclones progressively lose their proliferative capacity to become transient amplifying cells with limited growth (paraclones), a phenomenon termed clonal conversion. Although it negatively impacts the culture lifespan and the success of cell transplantation, little is known on the molecular mechanism underlying clonal conversion. Here, we show that holoclones and paraclones differ in their actin filament organization, with actin bundles distributed radially in holoclones and circumferentially in paraclones. Moreover, actin organization sets the stage for a differing response to epidermal growth factor (EGF), since EGF signalling induces a rapid expansion of colony size in holoclones and a significant reduction in paraclones. Furthermore, inhibition of PI3K or Rac1 in holoclones results in the reorganization of actin filaments in a pattern that is similar to that of paraclones. Importantly, continuous Rac1 inhibition in holoclones results in clonal conversion and reduction of growth potential. Together, our data connect loss of stem cells to EGF-induced colony dynamics governed by Rac1.
Pubmed
Web of science
Open Access
Yes
Create date
09/05/2013 13:52
Last modification date
20/08/2019 13:32
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