title: LSD1 is Required for Hair Cell Regeneration in Zebrafish.
abstract: Lysine-specific demethylase 1 (LSD1/KDM1A) plays an important role in complex cellular processes such as differentiation, proliferation, apoptosis, and cell cycle progression. It has recently been demonstrated that during development, downregulation of LSD1 inhibits cell proliferation, modulates the expression of cell cycle regulators, and reduces hair cell formation in the zebrafish lateral line, which suggests that LSD1-mediated epigenetic regulation plays a key role in the development of hair cells. However, the role of LSD1 in hair cell regeneration after hair cell loss remains poorly understood. Here, we demonstrate the effect of LSD1 on hair cell regeneration following neomycin-induced hair cell loss. We show that the LSD1 inhibitor trans-2-phenylcyclopropylamine (2-PCPA) significantly decreases the regeneration of hair cells in zebrafish after neomycin damage. In addition, immunofluorescent staining demonstrates that 2-PCPA administration suppresses supporting cell proliferation and alters cell cycle progression. Finally, in situ hybridization shows that 2-PCPA significantly downregulates the expression of genes related to Wnt/β-catenin and Fgf activation. Altogether, our data suggest that downregulation of LSD1 significantly decreases hair cell regeneration after neomycin-induced hair cell loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways. Thus, LSD1 plays a critical role in hair cell regeneration and might represent a novel biomarker and potential therapeutic approach for the treatment of hearing loss.
authors.affiliation: Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Tang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People's Republic of China.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Cai
authors.affiliation: Co-innovation Center of Neuroregeneration, Key Laboratory for Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu, 210096, People's Republic of China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chai
authors.affiliation: Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China. hwli@shmu.edu.cn.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People's Republic of China. hwli@shmu.edu.cn.|Institute of Stem Cell and Regeneration Medicine, Institute of Biomedical Science, Fudan University, Shanghai, People's Republic of China. hwli@shmu.edu.cn.|Key Laboratory of Hearing Science, Ministry of Health, EENT Hospital, Fudan University, Shanghai, People's Republic of China. hwli@shmu.edu.cn.
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism*; D056466:Histone Demethylases / Q000378:metabolism*; D017403:In Situ Hybridization; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D053403:Lateral Line System / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D014191:Tranylcypromine / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D014191:Tranylcypromine; D005346:Fibroblast Growth Factors; D056466:Histone Demethylases; C586489:KDM1A protein, zebrafish
keywords: Fgf signaling pathway; Hair cell; LSD1; Regeneration; Wnt signaling pathway; Zebrafish