Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cells
Abstract Induction of new hair follicles (HFs) may be an ultimate treatment goal for alopecia; however, functional cells with HF inductivity must be expanded in bulk for clinical use. In vitro culture conditions are completely different from the in vivo microenvironment. Although fetal and postnatal...
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| Format: | Article |
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Nature Portfolio
2021-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-03508-0 |
| _version_ | 1819096267929681920 |
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| author | Minji Park Sunhyae Jang Jin Ho Chung Ohsang Kwon Seong Jin Jo |
| author_facet | Minji Park Sunhyae Jang Jin Ho Chung Ohsang Kwon Seong Jin Jo |
| author_sort | Minji Park |
| collection | DOAJ |
| description | Abstract Induction of new hair follicles (HFs) may be an ultimate treatment goal for alopecia; however, functional cells with HF inductivity must be expanded in bulk for clinical use. In vitro culture conditions are completely different from the in vivo microenvironment. Although fetal and postnatal dermal cells (DCs) have the potential to induce HFs, they rapidly lose this HF inductivity during culture, accompanied by a drastic change in gene expression. This suggests that epigenetic regulation may be involved. Of the various histone deacetylases (HDACs), Class I HDACs are noteworthy because they are ubiquitously expressed and have the strongest deacetylase activity. This study revealed that DCs from postnatal mice rapidly lose HF inductivity and that this reduction is accompanied by a significant decrease in histone H3 acetylation. However, MS-275, an inhibitor of class I HDACs, preserves HF inductivity in DCs during culture, increasing alkaline phosphatase activity and upregulating HF inductive genes such as BMP4, HEY1, and WIF1. In addition, the inhibition of class I HDACs activates the Wnt signaling pathway, the most well-described molecular pathway in HF development, via increased histone H3 acetylation within the promoter region of the Wnt transcription factor LEF1. Our results suggest that class I HDACs could be a potential target for the neogenesis of HFs. |
| first_indexed | 2024-12-21T23:56:29Z |
| format | Article |
| id | doaj.art-35f2a562ba834977ae5fc209022897a8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T23:56:29Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-35f2a562ba834977ae5fc209022897a82022-12-21T18:45:49ZengNature PortfolioScientific Reports2045-23222021-12-0111111010.1038/s41598-021-03508-0Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cellsMinji Park0Sunhyae Jang1Jin Ho Chung2Ohsang Kwon3Seong Jin Jo4Department of Dermatology, Seoul National University College of MedicineDepartment of Dermatology, Seoul National University College of MedicineDepartment of Dermatology, Seoul National University College of MedicineDepartment of Dermatology, Seoul National University College of MedicineDepartment of Dermatology, Seoul National University College of MedicineAbstract Induction of new hair follicles (HFs) may be an ultimate treatment goal for alopecia; however, functional cells with HF inductivity must be expanded in bulk for clinical use. In vitro culture conditions are completely different from the in vivo microenvironment. Although fetal and postnatal dermal cells (DCs) have the potential to induce HFs, they rapidly lose this HF inductivity during culture, accompanied by a drastic change in gene expression. This suggests that epigenetic regulation may be involved. Of the various histone deacetylases (HDACs), Class I HDACs are noteworthy because they are ubiquitously expressed and have the strongest deacetylase activity. This study revealed that DCs from postnatal mice rapidly lose HF inductivity and that this reduction is accompanied by a significant decrease in histone H3 acetylation. However, MS-275, an inhibitor of class I HDACs, preserves HF inductivity in DCs during culture, increasing alkaline phosphatase activity and upregulating HF inductive genes such as BMP4, HEY1, and WIF1. In addition, the inhibition of class I HDACs activates the Wnt signaling pathway, the most well-described molecular pathway in HF development, via increased histone H3 acetylation within the promoter region of the Wnt transcription factor LEF1. Our results suggest that class I HDACs could be a potential target for the neogenesis of HFs.https://doi.org/10.1038/s41598-021-03508-0 |
| spellingShingle | Minji Park Sunhyae Jang Jin Ho Chung Ohsang Kwon Seong Jin Jo Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cells Scientific Reports |
| title | Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cells |
| title_full | Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cells |
| title_fullStr | Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cells |
| title_full_unstemmed | Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cells |
| title_short | Inhibition of class I HDACs preserves hair follicle inductivity in postnatal dermal cells |
| title_sort | inhibition of class i hdacs preserves hair follicle inductivity in postnatal dermal cells |
| url | https://doi.org/10.1038/s41598-021-03508-0 |
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