Evidence map›Paper›PMID 40600354›Full record

ArticleCell proliferation2026

Single-Nucleus Transcriptomics Uncovers Xaf1-Driven PANoptosis as a Therapeutic Target in Aminoglycoside-Induced Hearing Loss.

Xinlin Wang, Hairong Xiao, Jiheng Wu, Yanqin Lin, Yiheng Ao, Zixuan Ye, Xin Tan, Fanliang Kong, Xin Chen, Renjie Chai and 1 more

Abstract read
In one paragraph

Article in Cell proliferation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Xinlin WangDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Hairong XiaoDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Jiheng WuDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Yanqin LinDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Yiheng AoDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Zixuan YeDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Xin TanDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Fanliang KongDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Xin ChenDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Renjie ChaiDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.ORCID https://orcid.org/0000-0002-3885-543X
Shasha ZhangDepartment of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, China.ORCID https://orcid.org/0009-0004-7473-2922

Funding

Basic and Applied Basic Research Foundation of Guangdong Province 2024A1515010548China Ministry of Science and Technology Grant 2021ZD0203304China Postdoctoral Science Foundation 2021T140113National Key Research and Development Program of China 2021YFA1101300National Key Research and Development Program of China 2021YFA1101800National Key Research and Development Program of China 2022YFA0807000National Key Research and Development Program of China 2023YFA1801804National Key Research and Development Program of China 2024YFC2511100National Natural Science Foundation of China 82101236National Natural Science Foundation of China 82171149National Natural Science Foundation of China 82330033National Natural Science Foundation of China 82371166Shenzhen Science and Technology Program JCYJ20230807114700001STI2030-Major Projects 2022ZD0205400the Innovative Research Teams Project in Regular Higher Education Institutions of Guangdong Province 2024KCXTD052
6 · The paper itself

Abstract

Aminoglycoside antibiotics are essential in managing many life-threatening diseases. However, their derivatives, such as neomycin, are associated with severe side effects such as persistent sensorineural hearing loss. Therefore, it is essential to elucidate the molecular and biochemical mechanisms of aminoglycoside-induced ototoxicity and identify targets for alleviating ototoxic injury. Here, we provide a detailed cochlear cell atlas of neomycin-induced acute and chronic ototoxicity-related changes through single-nucleus RNA sequencing profiling. Utilising this cochlear cell atlas, we used the Augur and scDist algorithms to evaluate cell-type-specific susceptibility to neomycin injury. We observed aberrant expression of X-linked inhibitor of apoptosis (Xiap)-associated factor 1 (Xaf1) in neomycin-exposed cochleae using the cochlear cell atlas, and we identified a novel role for Xaf1 in facilitating PANoptosis through overexpression and knockdown assays in vitro. Finally, we assessed the protective role of Xaf1 against neomycin-induced ototoxicity by Xaf1 knockdown in cochlear hair cells using adeno-associated virus-based gene delivery. Mechanistically, Xaf1 orchestrates PANoptosis activation through direct interaction with and transcriptional regulation of ZBP1, establishing its hierarchical position upstream in the signalling cascade. This study presents detailed cochlear cellular maps of neomycin-induced ototoxicity and serves as a valuable resource for identifying transcriptome-wide disease-driving perturbations at the single-cell level. More importantly, we identified Xaf1 as a critical target for modulating the PANoptosis pathway, offering a promising treatment strategy for aminoglycoside-induced ototoxicity.

Indexed as

Adaptor Proteins, Signal TransducingAminoglycosidesCell NucleusHearing LossTranscriptomeAnimalsAnti-Bacterial AgentsCochleaHair Cells, AuditoryHumansMiceNeomycinRNA-Binding ProteinsAdaptor Proteins, Signal TransducingAminoglycosidesAnti-Bacterial AgentsNeomycinRNA-Binding Proteinshair cellneomycinPANoptosissnRNA‐seqXaf1

Identifiers

PMID40600354
PMCPMC12774624

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.