NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
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| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/45/12/632 |
| Summary: | 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 <i>NRG1</i> was high in human LESCs and decreased dramatically upon differentiation. Knockdown of <i>NRG1</i> significantly inhibited LESC proliferation and upregulated the expression of the terminal differentiation marker genes <i>KRT3</i>, <i>KRT12</i> and <i>CLU</i>. In addition, the scratch wound closure assay showed that knockdown of <i>NRG1</i> 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. |
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| ISSN: | 1467-3037 1467-3045 |