Journal article
WNT signaling determines tumorigenicity and function of ESC-derived retinal progenitors
The Journal of clinical investigation, v 123(4), pp 1647-1661
01 Apr 2013
PMID: 23524971
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Tumor formation constitutes a major obstacle to the clinical application of embryonic stem cell-derived (ESC-derived) cells. In an attempt to find major extracellular signaling and intrinsic factors controlling tumorigenicity and therapeutic functionality of transplanted ESC-derived retinal progenitor cells (ESC-RPCs), we evaluated multiple kinds of ESC-RPCs in a mouse retinal degeneration model and conducted genome-wide gene expression profiling. We identified canonical WNT signaling as a critical determinant for the tumorigenicity and therapeutic function of ESC-RPCs. The function of WNT signaling is primarily mediated by TCF7, which directly induces expression of Sox2 and Nestin. Inhibition of WNT signaling, over-expression of dominant-negative Tcf7, and silencing Tcf7, Sox2, or Nestin all resulted in drastically reduced tumor formation and substantially improved retinal integration and visual preservation in mice. These results demonstrate that the WNT signaling cascade plays a critical role in modulating the tumorigenicity and functionality of ESC-derived progenitors.
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Details
- Title
- WNT signaling determines tumorigenicity and function of ESC-derived retinal progenitors
- Creators
- Lu Cui - Shanghai Jiao Tong UniversityYuan Guan - Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200030, Peoples R ChinaZepeng Qu - Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200030, Peoples R ChinaJingfa Zhang - Tongji Univ, Shanghai Peoples Hosp 10, Dept Ophthalmol, Sch Med, Shanghai 200092, Peoples R ChinaBing Liao - Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200030, Peoples R ChinaBo Ma - Fudan Univ, Dept Ophthalmol, Eye Ear Nose Throat Hosp, Shanghai 200433, Peoples R ChinaJiang Qian - Fudan Univ, Dept Ophthalmol, Eye Ear Nose Throat Hosp, Shanghai 200433, Peoples R ChinaDangsheng Li - Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R ChinaWeiye Li - Drexel UniversityGuo-Tong Xu - Tongji Univ, Shanghai Peoples Hosp 10, Dept Ophthalmol, Sch Med, Shanghai 200092, Peoples R ChinaYing Jin - Shanghai Jiao Tong University
- Publication Details
- The Journal of clinical investigation, v 123(4), pp 1647-1661
- Publisher
- Amer Soc Clinical Investigation Inc
- Number of pages
- 15
- Grant note
- 2010CB945200; 2011DFB30010; 2011CB965101; 2013CB966801; 2009CB941103 / National High Technology Research and Development Program of China XDA01010102 / Chinese Academy of Science; Chinese Academy of Sciences 91019023; 31000639; 31171419 / National Natural Science Foundation; National Natural Science Foundation of China (NSFC) S30201 / Shanghai Leading Academic Discipline Project
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Ophthalmology [Historical]
- Web of Science ID
- WOS:000317021800026
- Scopus ID
- 2-s2.0-84875827492
- Other Identifier
- 991019167654904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental