Cochlear nucleus spatial transcriptomes of normal and hearing loss mice reveal a critical role of Spp1 in bushy cells
The molecular and cellular mechanisms underlying the function of the cochlear nucleus (CN) remain to be fully elucidated. Using single-nucleus RNA sequencing and single-cell spatial transcriptome analyses, we generated a comprehensive cell type atlas of the mouse CN, identified molecularly defined CN subregions, and quantified changes in gene expression and the spatial organization of CN cells in normal mice during postnatal development and in mutant mice with congenital hearing loss. We further identified a subtype of bushy cells expressing the osteopontin-encoding gene Spp1 as the primary CN cell type that exhibited hearing loss-induced alteration of gene expression. Among the highly affected genes in bushy cells, deletion of the auditory input-regulated gene Spp1 affected CN processing of auditory signals in mice. These results provide the most comprehensive cellular and molecular database to date for understanding auditory processing within the CN and identifying potential therapeutic targets for hearing restoration at the CN level.
Authors
- Junpu Mei (ORCID: https://orcid.org/0000-0003-4630-0765)
- Ningyuan Zhu (ORCID: https://orcid.org/0000-0003-3767-3578)
- Sidi Liu (ORCID: https://orcid.org/0000-0003-4000-6098)
- Ruijie Cai
- Xingle Zhao (ORCID: https://orcid.org/0000-0002-3992-2139)
- Meijian Wang (ORCID: https://orcid.org/0000-0001-6359-6137)
- Ke Liu (ORCID: https://orcid.org/0000-0002-0505-920X)
- Xiaowei Li (ORCID: https://orcid.org/0000-0003-2032-4742)
- Shangfeng Liao
- Mu-ming Poo
- Hao Wu
- Lei Song
- Yuanwei Zhang
- Ying Chen
- Li Song
- Shaohui Lin
- Xiaotong Ma
- Lijian Zhao
- Jing Zhao
- Weijun Zhou
Institutions
- BGI Group (China) (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Shanghai Mental Health Center (CN)
- Shanghai Ninth People's Hospital (CN)
- Center for Excellence in Brain Science and Intelligence Technology (CN)
- Guangdong Academy of Medical Sciences (CN)
- Sanya University (CN)
- Guangdong Provincial People's Hospital (CN)
- Shanghai Clinical Research Center (CN)
- BGI Research (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- Cell Research
- Published
- 2026-04-06
- DOI
- https://doi.org/10.1038/s41422-026-01246-4
- Primary Topic
- Hearing, Cochlea, Tinnitus, Genetics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality