NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells
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Published:2023-12-14
Issue:12
Volume:45
Page:10121-10130
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ISSN:1467-3045
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Container-title:Current Issues in Molecular Biology
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language:en
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Short-container-title:CIMB
Author:
Wang Bofeng1, Guo Huizhen1, Han Zhuo1, Wu Siqi1, Liu Jiafeng1, Lin Zesong1, An Fengjiao1, Zhu Jin1, Li Mingsen1
Affiliation:
1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China
Abstract
Limbal epithelial stem/progenitor cells (LESCs) proliferate, migrate and differentiate into mature corneal epithelium cells (CECs) that cover the ocular surface. LESCs play a crucial role in the maintenance and regeneration of the corneal epithelium, and their dysfunction can lead to various corneal diseases. Neuregulin 1 (NRG1) is a member of the epidermal growth factor family that regulates the growth and differentiation of epithelial tissues. Here, we depicted the dynamic transcriptomic profiles during human CEC differentiation, identifying six gene co-expression modules that were specific to different differentiation stages. We found that the expression of NRG1 was high in human LESCs and decreased dramatically upon differentiation. Knockdown of NRG1 significantly inhibited LESC proliferation and upregulated the expression of the terminal differentiation marker genes KRT3, KRT12 and CLU. In addition, the scratch wound closure assay showed that knockdown of NRG1 attenuated wound closure of LESCs over 24 h. Together, we dissected the transcriptional regulatory dynamics during CEC differentiation and identified NRG1 as a key regulator that promoted LESC proliferation and migration and maintained the undifferentiated state.
Funder
Guangzhou Science and Technology Plan Project
Subject
Microbiology (medical),Molecular Biology,General Medicine,Microbiology
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