Show simple item record

dc.contributor.authorLu, Rong
dc.contributor.authorQu, Yangluowa
dc.contributor.author瞿杨洛娃
dc.contributor.authorGe, Jian
dc.contributor.authorZhang, Lili
dc.contributor.authorSu, Zhitao
dc.contributor.authorPflugfelder, Stephen C.
dc.contributor.authorLi, De-Quan
dc.date.accessioned2013-04-16T07:10:00Z
dc.date.available2013-04-16T07:10:00Z
dc.date.issued2012-04
dc.identifier.citationSTEM CELLS,2012,30(4):753-761zh_CN
dc.identifier.issn1066-5099
dc.identifier.urihttp://dx.doi.org/10.1002/stem.1032
dc.identifier.uriWOS:000302005000018
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/15649
dc.description.abstractTCF4, a key transcription factor of Wnt signaling system, has been recently found to be essential for maintaining stem cells. However, its signaling pathway is not well elucidated. This study was to explore the functional roles and signaling pathway of TCF4 in maintaining adult stem cell properties using human corneal epithelial stem cells as a model. With immunofluorescent staining and real-time polymerase chain reaction, we observed that TCF4 was exclusively expressed in the basal layer of human limbal epithelium where corneal epithelial stem cells reside. TCF4 was found to be well colocalized with ABCG2 and p63, two recognized epithelial stem/progenitor cell markers. Using in vitro culture models of primary human corneal epithelial cells, we revealed that TCF4 mRNA and protein were upregulated by cells in exponential growth stage, and RNA interference by small interfering RNA-TCF4 (10-50 nM) transfection blocked TCF4 signaling and suppressed cell proliferation as measured by WST-1 assay. TCF4 silence was found to be accompanied by downregulated proliferation-associated factors p63 and survivin, as well as upregulated cyclin-dependent kinase inhibitor 1C (p57). By creating a wound healing model in vitro, we identified upregulation and activation of beta-catenin/TCF4 with their protein translocation from cytoplasm to nuclei, as evaluated by reverse transcription-quantitative real-time polymerase chain reaction, immunostaining, and Western blotting. Upregulated p63/survivin and downregulated p57 were further identified to be TCF4 downstream molecules that promote cell migration and proliferation in wound healing process. These findings demonstrate that transcription factor TCF4 plays an important role in determining or maintaining the phenotype and functional properties of human corneal epithelial stem cells. STEM CELLS 2012; 30:753761zh_CN
dc.description.sponsorshipDOD CDMRP [FY06 PR064719]; NIH [EY11915]; National Natural Science Foundation of China [30901634]; Fight for Sight; Research to Prevent Blindness, Oshman Foundationzh_CN
dc.language.isoenzh_CN
dc.publisherWILEY-BLACKWELLzh_CN
dc.subjectAdult stem cellzh_CN
dc.subjectCorneal epitheliumzh_CN
dc.subjectTCF4zh_CN
dc.subjectSurvivinzh_CN
dc.subjectProliferationzh_CN
dc.titleTranscription Factor TCF4 Maintains the Properties of Human Corneal Epithelial Stem Cellszh_CN
dc.typeArticlezh_CN


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record