First Author | Ouji Y | Year | 2015 |
Journal | J Invest Dermatol | Volume | 135 |
Issue | 6 | Pages | 1598-1608 |
PubMed ID | 25437427 | Mgi Jnum | J:221069 |
Mgi Id | MGI:5637884 | Doi | 10.1038/jid.2014.510 |
Citation | Ouji Y, et al. (2015) Partial maintenance and long-term expansion of murine skin epithelial stem cells by wnt-3a in vitro. J Invest Dermatol 135(6):1598-608 |
abstractText | CD49f(+)CD34(+) cells, a skin epithelial stem cell (EpSC)-rich population, were prepared from adult mouse skin and cultured in the presence of Wnt-3a without feeder cells. CD34 expression was retained in about 10% of the cells, which had proliferated about 1,000-fold by day 10, although completely lost by day 14. CD49f(+)CD34(+) cells sorted on day 10 retained canonical Wnt-responsiveness, proliferated markedly in the presence of Wnt-3a, maintained undifferentiated epithelial cell marker expression, and promoted hair follicle development in vivo. Those were subjected to a second 10-day culture with Wnt-3a and sorted, and then the same procedures were repeated a total of 15 times. CD49f(+)CD34(+) cells obtained from each of those cultures retained the same EpSC characteristics as the original cells. CD34(+) and CD34(-) cells were found to produce Wnt-3a and Wnt/beta-catenin inhibitors, respectively. CD34(+) cells resided as small cellular clusters surrounded by a large amount of CD34(-) cells. Furthermore, we found that exogenous Wnt-3a delayed the conversion of CD34(+) cells to CD34(-) cells and induced CD34(-) cells to suppress the production of Wnt/beta-catenin inhibitors, likely leading to generation of a microenvironment favorable for maintaining EpSCs. Our results suggest the possibility of partial long-term maintenance of EpSCs in vitro by Wnt-3a. |