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...
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MDPI AG
2023-12-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/12/632 |
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| author | Bofeng Wang Huizhen Guo Zhuo Han Siqi Wu Jiafeng Liu Zesong Lin Fengjiao An Jin Zhu Mingsen Li |
| author_facet | Bofeng Wang Huizhen Guo Zhuo Han Siqi Wu Jiafeng Liu Zesong Lin Fengjiao An Jin Zhu Mingsen Li |
| author_sort | Bofeng Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T20:53:43Z |
| format | Article |
| id | doaj.art-71ea816d080d49afaf53a63f6fcb458b |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-08T20:53:43Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-71ea816d080d49afaf53a63f6fcb458b2023-12-22T14:00:45ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-12-014512101211013010.3390/cimb45120632NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem CellsBofeng Wang0Huizhen Guo1Zhuo Han2Siqi Wu3Jiafeng Liu4Zesong Lin5Fengjiao An6Jin Zhu7Mingsen Li8State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaLimbal 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.https://www.mdpi.com/1467-3045/45/12/632limbal epithelial stem cellsgene expression dynamicsproliferationdifferentiationmigration |
| spellingShingle | Bofeng Wang Huizhen Guo Zhuo Han Siqi Wu Jiafeng Liu Zesong Lin Fengjiao An Jin Zhu Mingsen Li NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells Current Issues in Molecular Biology limbal epithelial stem cells gene expression dynamics proliferation differentiation migration |
| title | NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells |
| title_full | NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells |
| title_fullStr | NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells |
| title_full_unstemmed | NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells |
| title_short | NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells |
| title_sort | nrg1 regulates proliferation migration and differentiation of human limbal epithelial stem cells |
| topic | limbal epithelial stem cells gene expression dynamics proliferation differentiation migration |
| url | https://www.mdpi.com/1467-3045/45/12/632 |
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