Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone
In the adult mammalian brain, neurons are produced from neural stem cells (NSCs) residing in two niches—the subventricular zone (SVZ), which forms the lining of the lateral ventricles, and the subgranular zone in the hippocampus. Epigenetic mechanisms contribute to maintaining distinct cell fates by...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/5/2540 |
| _version_ | 1797264414829707264 |
|---|---|
| author | Momoko Fukuda Yuki Fujita Yuko Hino Mitsuyoshi Nakao Katsuhiko Shirahige Toshihide Yamashita |
| author_facet | Momoko Fukuda Yuki Fujita Yuko Hino Mitsuyoshi Nakao Katsuhiko Shirahige Toshihide Yamashita |
| author_sort | Momoko Fukuda |
| collection | DOAJ |
| description | In the adult mammalian brain, neurons are produced from neural stem cells (NSCs) residing in two niches—the subventricular zone (SVZ), which forms the lining of the lateral ventricles, and the subgranular zone in the hippocampus. Epigenetic mechanisms contribute to maintaining distinct cell fates by suppressing gene expression that is required for deciding alternate cell fates. Several histone deacetylase (HDAC) inhibitors can affect adult neurogenesis in vivo. However, data regarding the role of specific HDACs in cell fate decisions remain limited. Herein, we demonstrate that HDAC8 participates in the regulation of the proliferation and differentiation of NSCs/neural progenitor cells (NPCs) in the adult mouse SVZ. Specific knockout of <i>Hdac8</i> in NSCs/NPCs inhibited proliferation and neural differentiation. Treatment with the selective HDAC8 inhibitor PCI-34051 reduced the neurosphere size in cultures from the SVZ of adult mice. Further transcriptional datasets revealed that HDAC8 inhibition in adult SVZ cells disturbs biological processes, transcription factor networks, and key regulatory pathways. HDAC8 inhibition in adult SVZ neurospheres upregulated the cytokine-mediated signaling and downregulated the cell cycle pathway. In conclusion, HDAC8 participates in the regulation of in vivo proliferation and differentiation of NSCs/NPCs in the adult SVZ, which provides insights into the underlying molecular mechanisms. |
| first_indexed | 2024-04-25T00:28:32Z |
| format | Article |
| id | doaj.art-15fcb06710cc4a1dbc1e253a5b724828 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:28:32Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-15fcb06710cc4a1dbc1e253a5b7248282024-03-12T16:45:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01255254010.3390/ijms25052540Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular ZoneMomoko Fukuda0Yuki Fujita1Yuko Hino2Mitsuyoshi Nakao3Katsuhiko Shirahige4Toshihide Yamashita5Department of Anatomy and Developmental Biology, School of Medicine, Shimane University, 89-1, Enya-cho, Izumo-shi 693-8501, JapanDepartment of Anatomy and Developmental Biology, School of Medicine, Shimane University, 89-1, Enya-cho, Izumo-shi 693-8501, JapanInstitute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, JapanInstitute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, JapanLaboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, JapanDepartment of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita 565-0871, JapanIn the adult mammalian brain, neurons are produced from neural stem cells (NSCs) residing in two niches—the subventricular zone (SVZ), which forms the lining of the lateral ventricles, and the subgranular zone in the hippocampus. Epigenetic mechanisms contribute to maintaining distinct cell fates by suppressing gene expression that is required for deciding alternate cell fates. Several histone deacetylase (HDAC) inhibitors can affect adult neurogenesis in vivo. However, data regarding the role of specific HDACs in cell fate decisions remain limited. Herein, we demonstrate that HDAC8 participates in the regulation of the proliferation and differentiation of NSCs/neural progenitor cells (NPCs) in the adult mouse SVZ. Specific knockout of <i>Hdac8</i> in NSCs/NPCs inhibited proliferation and neural differentiation. Treatment with the selective HDAC8 inhibitor PCI-34051 reduced the neurosphere size in cultures from the SVZ of adult mice. Further transcriptional datasets revealed that HDAC8 inhibition in adult SVZ cells disturbs biological processes, transcription factor networks, and key regulatory pathways. HDAC8 inhibition in adult SVZ neurospheres upregulated the cytokine-mediated signaling and downregulated the cell cycle pathway. In conclusion, HDAC8 participates in the regulation of in vivo proliferation and differentiation of NSCs/NPCs in the adult SVZ, which provides insights into the underlying molecular mechanisms.https://www.mdpi.com/1422-0067/25/5/2540adult neurogenesisneural stem cellshistone deacetylase 8 (HDAC8)cytokine-mediated signalingsubventricular zone |
| spellingShingle | Momoko Fukuda Yuki Fujita Yuko Hino Mitsuyoshi Nakao Katsuhiko Shirahige Toshihide Yamashita Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone International Journal of Molecular Sciences adult neurogenesis neural stem cells histone deacetylase 8 (HDAC8) cytokine-mediated signaling subventricular zone |
| title | Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone |
| title_full | Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone |
| title_fullStr | Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone |
| title_full_unstemmed | Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone |
| title_short | Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone |
| title_sort | inhibition of hdac8 reduces the proliferation of adult neural stem cells in the subventricular zone |
| topic | adult neurogenesis neural stem cells histone deacetylase 8 (HDAC8) cytokine-mediated signaling subventricular zone |
| url | https://www.mdpi.com/1422-0067/25/5/2540 |
| work_keys_str_mv | AT momokofukuda inhibitionofhdac8reducestheproliferationofadultneuralstemcellsinthesubventricularzone AT yukifujita inhibitionofhdac8reducestheproliferationofadultneuralstemcellsinthesubventricularzone AT yukohino inhibitionofhdac8reducestheproliferationofadultneuralstemcellsinthesubventricularzone AT mitsuyoshinakao inhibitionofhdac8reducestheproliferationofadultneuralstemcellsinthesubventricularzone AT katsuhikoshirahige inhibitionofhdac8reducestheproliferationofadultneuralstemcellsinthesubventricularzone AT toshihideyamashita inhibitionofhdac8reducestheproliferationofadultneuralstemcellsinthesubventricularzone |