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学科主题: 临床医学
题名:
The beta-catenin/Tcf4/survivin signaling maintains a less differentiated phenotype and high proliferative capacity of human corneal epithelial progenitor cells
作者: Lu, Rong1,2; Bian, Fang1,3; Zhang, Xiaobo1,4; Qi, Hong1,5; Chuang, Eliseu Y.1; Pflugfelder, Stephen C.1; Li, De-Quan1
关键词: Adult stem cell ; Stem cell niche ; Corneal epithelium ; beta-Catenin ; Tcf4 ; Survivin
刊名: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
发表日期: 2011-05-01
DOI: 10.1016/j.biocel.2011.01.018
卷: 43, 期:5, 页:751-759
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
英文摘要:

It is clear that the microenvironment or niche plays an important role in determining the fate of stem cells: being stem cells or differentiated. However, the intrinsic pathways controlling the fate of adult stem cells in different niches are largely unknown. This study was to explore the role of beta-catenin/Tcf4/survivin signaling in determining the fate of human corneal epithelial stem cells in different media. We observed that the low calcium serum-free media, especially CnT-20, promoted proliferative capacity, colony forming efficiency and stem cell-like phenotype of human corneal epithelial cells (HCECs) when compared with the cells cultured in a high calcium serum-containing medium SHEM. Three key factors in Wnt signaling, beta-catenin, Tcf4 and survivin, were found to be expressed higher by HCECs grown in CnT-20 than those cultured in SHEM, as evaluated by real-time PCR, Western blotting and immunostaining. Transfection of siRNA-Tcf4 at 10-50 nM knocked down Tcf4, and also significantly suppressed its down stream molecule survivin at both mRNA and protein levels in HCECs. Furthermore, Tcf4 silencing significantly suppressed the proliferative capacity of HCECs, measured by WST-1 assay, compared with the control groups, untreated or transfected with non-coding sequence siRNA-fluorescein. These findings demonstrate that low calcium serum free media promote ex vivo expansion of corneal epithelial progenitor cells that retain a less differentiated phenotype and high proliferative capacity via beta-catenin/Tcf4/survivin signaling, a novel intrinsic pathway. This study may have high impact and clinic implication on the expansion of corneal epithelial stem cells in regenerative medicine, especially for ocular surface reconstruction. (C) 2011 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: CDMRP PRMRP FY06 PR064719 ; EY11915 ; 30901634 ; 30872813 ; 9151008901000210
项目资助者: Department of Defense ; NEI NIH ; National Natural Science Foundation of China ; Natural Science Foundation of Guangdong Province ; Lions Foundation for Sight ; Research to Prevent Blindness ; Oshman Foundation ; William Stamps Farish Fund
WOS记录号: WOS:000290011900009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50725
Appears in Collections:北京大学第三临床医学院_眼科_期刊论文

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作者单位: 1.Baylor Coll Med, Ocular Surface Ctr, Cullen Eye Inst, Dept Ophthalmol, Houston, TX 77030 USA
2.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China
3.Huazhong Sci & Technol Univ, Union Hosp, Dept Ophthalmol, Tongji Med Coll, Wuhan, Peoples R China
4.Wenzhou Med Coll, Sch Ophthalmol & Optometry, Hosp Eye, Wenzhou, Peoples R China
5.Peking Univ, Hosp 3, Dept Ophthalmol, Beijing 100871, Peoples R China

Recommended Citation:
Lu, Rong,Bian, Fang,Zhang, Xiaobo,et al. The beta-catenin/Tcf4/survivin signaling maintains a less differentiated phenotype and high proliferative capacity of human corneal epithelial progenitor cells[J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2011,43(5):751-759.
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