Direct reprogramming of fibroblasts into spiral ganglion neurons by defined transcription factors.

Autor: Huang Y; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, China., Chen Z; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, China., Chen J; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, China.; Department of Neurology, The Affiliated Drum Tower Hospital of Medical School and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China., Liu J; National Institute of Biological Sciences, Beijing, China.; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China., Qiu C; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, China., Liu Q; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, China.; Research Institute of Otolaryngology, Nanjing, China., Zhang L; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, China., Zhu GJ; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; Research Institute of Otolaryngology, Nanjing, China., Ma X; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; Research Institute of Otolaryngology, Nanjing, China., Sun S; National Institute of Biological Sciences, Beijing, China.; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China., Shi YS; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, China.; Guangdong Institute of Intelligence Science and Technology, Zhuhai, China., Wan G; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, China.; Research Institute of Otolaryngology, Nanjing, China.
Jazyk: angličtina
Zdroj: Cell proliferation [Cell Prolif] 2024 Nov 17, pp. e13775. Date of Electronic Publication: 2024 Nov 17.
DOI: 10.1111/cpr.13775
Abstrakt: Degeneration of the cochlear spiral ganglion neurons (SGNs) is one of the major causes of sensorineural hearing loss and significantly impacts the outcomes of cochlear implantation. Functional regeneration of SGNs holds great promise for treating sensorineural hearing loss. In this study, we systematically screened 33 transcriptional regulators implicated in neuronal and SGN fate. Using gene expression array and principal component analyses, we identified a sequential combination of Ascl1, Pou4f1 and Myt1l (APM) in promoting functional reprogramming of SGNs. The neurons induced by APM expressed mature neuronal and SGN lineage-specific markers, displayed mature SGN-like electrophysiological characteristics and exhibited single-cell transcriptomes resembling the endogenous SGNs. Thus, transcription factors APM may serve as novel candidates for direct reprogramming of SGNs and hearing recovery due to SGN damages.
(© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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