Abstract

The corneal epithelium is consistently regenerated by limbal stem/progenitor cells (LSCs), a very small population of adult stem cells residing in the limbus. Several Wnt ligands, including Wnt6, are preferentially expressed in the limbus. To investigate the role of Wnt6 in regulating proliferation and maintenance of human LSCs in an in vitro LSC expansion setting, we generated NIH-3T3 feeder cells to overexpress different levels of Wnt6. Characterization of LSCs cultured on Wnt6 expressing 3T3 cells showed that high level of Wnt6 increased proliferation of LSCs. Medium and high levels of Wnt6 also increased the percentage of small cells (diameter ≤ 12 µm), a feature of the stem cell population. Additionally, the percentage of cells expressing the differentiation marker K12 was significantly reduced in the presence of medium and high Wnt6 levels. Although Wnt6 is mostly known as a canonical Wnt ligand, our data showed that canonical and non-canonical Wnt signaling pathways were activated in the Wnt6-supplemented LSC cultures, a finding suggesting that interrelationships between both pathways are required for LSC regulation.

Details

Title
Wnt6 plays a complex role in maintaining human limbal stem/progenitor cells
Author
Bonnet Clémence 1 ; Oh, Denise 2 ; Hua, Mei 3 ; Robertson, Sarah 2 ; Chang, Derek 2 ; Jean-Louis, Bourges 4 ; Behar-Cohen, Francine 4 ; Zheng, Jie J 5 ; Deng, Sophie X 5 

 University of California, Los Angeles, Stein Eye Institute, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); Paris University, Centre de Recherche des Cordeliers, and Ophthalmology Department, Cochin Hospital, AP-HP, INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893) 
 University of California, Los Angeles, Stein Eye Institute, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
 University of North Carolina, Department of Ophthalmology, Chapel Hill, USA (GRID:grid.410711.2) (ISNI:0000 0001 1034 1720) 
 Paris University, Centre de Recherche des Cordeliers, and Ophthalmology Department, Cochin Hospital, AP-HP, INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893) 
 University of California, Los Angeles, Stein Eye Institute, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); University of California, Molecular Biology Institute, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2584645795
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.