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LSC proliferation and differentiation are essential for corneal homeostasis, however, the regulatory mechanism remains largely unexplored. Here, we performed single\u2010cell RNA sequencing and discovered proliferation heterogeneity as well as spontaneously differentiated and senescent cell subgroups in multiply passaged primary LSC. Fasciculation and elongation protein zeta 1 (FEZ1) and Dickkopf\u20101 (DKK1) were identified as two significant regulators of LSC proliferation and senescence. These two factors were mainly expressed in undifferentiated corneal epithelial cells (CECs). Knocking down the expression of either FEZ1 or DKK1 reduced cell division and caused cell cycle arrest. We observed that DKK1 acted as a downstream target of FEZ1 in LSC and that exogenous DKK1 protein partially prevented growth arrest and senescence upon FEZ1 suppression in vitro. In a mouse model of corneal injury, DKK1 also rescued the corneal epithelium after recovery was inhibited by FEZ1 suppression. Hence, the FEZ1\u2013DKK1 axis was required for CEC proliferation and the juvenile state and can potentially be targeted as a therapeutic strategy for promoting recovery after corneal injury.<\/jats:p>","DOI":"10.1111\/cpr.13433","type":"journal-article","created":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T06:40:07Z","timestamp":1677998407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Single\u2010cell transcriptomics implicates the <scp>FEZ1\u2013DKK1<\/scp> axis in the regulation of corneal epithelial cell proliferation and senescence"],"prefix":"10.1111","volume":"56","author":[{"given":"Liqiong","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat\u2010sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science|  Guangzhou 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