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Here, we aimed to explore its underlying molecular mechanism and evaluate its potential in the treatment of limbal stem cell deficiency (LSCD). Based on the findings of mRNA\u2010sequencing, the expression of key molecules in WNT\/calcineurin A\/NFATC2 signalling pathway was investigated in WNT16b\u2010co\u2010incubated hLESCs and control hLESCs. An epithelial wound healing model was established on Wnt16b\u2010KO mice to confirm the regulatory effect of WNT16b in vivo. The therapeutic potential of WNT16b\u2010co\u2010incubated hLESCs was also evaluated in mice with LSCD. Our findings showed that WNT16b bound with Frizzled7, promoted the release of Ca<jats:sup>2+<\/jats:sup> and activated calcineurin A and NFATC2. With the translocation of NFATC2 into cell nucleus and the activation of HDAC3, WDR5 and GCN5L2, the expression of H3K4me3, H3K14ac and H3K27ac in the promoter regions of FoxM1 and c\u2010MYC increased, which led to hLESC proliferation. The effect of the WNT16b\/calcium\/calcineurin A\/NFATC2 pathway on LESC homeostasis maintenance and corneal epithelial repair was confirmed in Wnt16b\u2010KO mice. Moreover, WNT16b\u2010coincubated hLESCs could reconstruct a stable ocular surface and inhibit corneal neovascularization in mice with LSCD. In conclusion, WNT16b enhances the proliferation and maintains the stemness of hLESCs by activating the non\u2010canonical calcium\/calcineurin A\/NFATC2 pathway in vitro and in vivo<jats:italic>,<\/jats:italic> and accelerates corneal epithelial wound healing.<\/jats:p>","DOI":"10.1111\/cpr.13460","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T05:57:17Z","timestamp":1679983037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp>WNT16b<\/scp> promotes the proliferation and <scp>self\u2010renewal<\/scp> of human limbal epithelial stem\/progenitor cells via activating the calcium\/calcineurin A\/<scp>NFATC2<\/scp> pathway"],"prefix":"10.1111","volume":"56","author":[{"given":"Xichen","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Eye, Ear, Nose and Throat Hospital of Fudan University  Fudan 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