Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells
Abstract The Jun dimerization protein (Jdp2) gene is active in mouse cerebellar granule cells and its protein product plays a crucial role in the formation of the cerebellum lobes through programmed cell death. However, the role of Jdp2 in cellular differentiation and pluripotency in the cerebellum,...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-12-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-024-02262-2 |
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| author | Chia-Chen Ku Jia-Bin Pan Kenly Wuputra Wen-Li Hsu Kohsuke Kato Michiya Noguchi Yukio Nakamura Shigeo Saito Cheng-Yu Tsai Ying-Chu Lin Deng-Chyang Wu Chang-Shen Lin Kazunari K. Yokoyama |
| author_facet | Chia-Chen Ku Jia-Bin Pan Kenly Wuputra Wen-Li Hsu Kohsuke Kato Michiya Noguchi Yukio Nakamura Shigeo Saito Cheng-Yu Tsai Ying-Chu Lin Deng-Chyang Wu Chang-Shen Lin Kazunari K. Yokoyama |
| author_sort | Chia-Chen Ku |
| collection | DOAJ |
| description | Abstract The Jun dimerization protein (Jdp2) gene is active in mouse cerebellar granule cells and its protein product plays a crucial role in the formation of the cerebellum lobes through programmed cell death. However, the role of Jdp2 in cellular differentiation and pluripotency in the cerebellum, and the effect of the antioxidation reaction on cell plasticity, remain unknown. N-acetyl-l-cysteine (NAC) induced the early commitment of the differentiation of granule cell precursors (GCPs) to neurons, especially Purkinje cells, via the γ-aminobutyric acid type A receptor α6 subunit (Gabra6) axis; moreover, Jdp2 depletion enhanced this differentiation program of GCPs. The antioxidative effect of NAC was the main driving force of this decision toward the neural differentiation of the GCP population in the presence of Gabra6 in vitro. This implies that antioxidative drugs are effective agents for rescuing oxidative-stress-induced GCP damages in the cerebellum and commit this Gabra6-positive cell population toward differentiation into Purkinje cells. |
| format | Article |
| id | doaj-art-506c16cb1f2d453ab91d4cdf8c349474 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-506c16cb1f2d453ab91d4cdf8c3494742024-12-22T12:15:34ZengNature Publishing GroupCell Death Discovery2058-77162024-12-0110111210.1038/s41420-024-02262-2Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cellsChia-Chen Ku0Jia-Bin Pan1Kenly Wuputra2Wen-Li Hsu3Kohsuke Kato4Michiya Noguchi5Yukio Nakamura6Shigeo Saito7Cheng-Yu Tsai8Ying-Chu Lin9Deng-Chyang Wu10Chang-Shen Lin11Kazunari K. Yokoyama12Graduate Institute of Medicine, Kaohsiung Medical UniversityGraduate Institute of Medicine, Kaohsiung Medical UniversityGraduate Institute of Medicine, Kaohsiung Medical UniversityRegenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical UniversityDepartment of Infection Biology, Graduate School of Comprehensive Human Sciences, the University of TsukubaCell Engineering Division, RIKEN BioResource Research CenterCell Engineering Division, RIKEN BioResource Research CenterSaito Laboratory of Cell TechnologyGraduate Institute of Medicine, Kaohsiung Medical UniversitySchool of Dentistry, Kaohsiung Medical UniversityRegenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical UniversityGraduate Institute of Medicine, Kaohsiung Medical UniversityGraduate Institute of Medicine, Kaohsiung Medical UniversityAbstract The Jun dimerization protein (Jdp2) gene is active in mouse cerebellar granule cells and its protein product plays a crucial role in the formation of the cerebellum lobes through programmed cell death. However, the role of Jdp2 in cellular differentiation and pluripotency in the cerebellum, and the effect of the antioxidation reaction on cell plasticity, remain unknown. N-acetyl-l-cysteine (NAC) induced the early commitment of the differentiation of granule cell precursors (GCPs) to neurons, especially Purkinje cells, via the γ-aminobutyric acid type A receptor α6 subunit (Gabra6) axis; moreover, Jdp2 depletion enhanced this differentiation program of GCPs. The antioxidative effect of NAC was the main driving force of this decision toward the neural differentiation of the GCP population in the presence of Gabra6 in vitro. This implies that antioxidative drugs are effective agents for rescuing oxidative-stress-induced GCP damages in the cerebellum and commit this Gabra6-positive cell population toward differentiation into Purkinje cells.https://doi.org/10.1038/s41420-024-02262-2 |
| spellingShingle | Chia-Chen Ku Jia-Bin Pan Kenly Wuputra Wen-Li Hsu Kohsuke Kato Michiya Noguchi Yukio Nakamura Shigeo Saito Cheng-Yu Tsai Ying-Chu Lin Deng-Chyang Wu Chang-Shen Lin Kazunari K. Yokoyama Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells Cell Death Discovery |
| title | Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells |
| title_full | Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells |
| title_fullStr | Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells |
| title_full_unstemmed | Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells |
| title_short | Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells |
| title_sort | trans differentiation of jdp2 depleted gaba receptor positive cerebellar granule cells to purkinje cells |
| url | https://doi.org/10.1038/s41420-024-02262-2 |
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