Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells

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

doi:10.1038/s41420-024-02262-2

Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells

Cell Death Discov. 2024 Dec 18;10(1):500. doi: 10.1038/s41420-024-02262-2.

Authors

Chia-Chen Ku^{1

2

3}, Jia-Bin Pan^{1

2

3}, Kenly Wuputra^{1

2

3}, Wen-Li Hsu^{2

4

5}, Kohsuke Kato⁶, Michiya Noguchi⁷, Yukio Nakamura⁷, Shigeo Saito⁸, Cheng-Yu Tsai^{1

9

10

11}, Ying-Chu Lin¹², Deng-Chyang Wu^{13

14}, Chang-Shen Lin^{1

15}, Kazunari K Yokoyama^{16

17

18}

Affiliations

¹ Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁴ Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁵ National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin County, Taiwan.
⁶ Department of Infection Biology, Graduate School of Comprehensive Human Sciences, the University of Tsukuba, Tsukuba, Japan.
⁷ Cell Engineering Division, RIKEN BioResource Research Center, Tsukuba, Ibaraki, Japan.
⁸ Saito Laboratory of Cell Technology, Yaita, Tochigi, Japan.
⁹ Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
¹⁰ Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, Taiwan.
¹¹ Department of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹² School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹³ Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. dechwu@kmu.edu.tw.
¹⁴ Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. dechwu@kmu.edu.tw.
¹⁵ Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
¹⁶ Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. kazu@kmu.edu.tw.
¹⁷ Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. kazu@kmu.edu.tw.
¹⁸ Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. kazu@kmu.edu.tw.

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.

Abstract

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