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Single-cell transcriptomic atlas of mouse cochlear aging.

ABSTRACT: Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.

SUBMITTER: Sun G

PROVIDER: S-EPMC10098046 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Single-cell transcriptomic atlas of mouse cochlear aging.

Sun Guoqiang G Zheng Yandong Y Fu Xiaolong X Zhang Weiqi W Ren Jie J Ma Shuai S Sun Shuhui S He Xiaojuan X Wang Qiaoran Q Ji Zhejun Z Cheng Fang F Yan Kaowen K Liu Ziyi Z Belmonte Juan Carlos Izpisua JCI Qu Jing J Wang Si S Chai Renjie R Liu Guang-Hui GH

Protein & cell 20230401 3

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptos ...[more]

PMID: 36933008

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Project description:IntroductionAdvanced paternal age of reproduction is an increasing trend, especially in developed countries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fertility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging-associated molecular and cellular alterations in testicular tissue is still missing.ObjectivesWe aimed to dissect aging-associated molecular characteristics in testes of mice.MethodsSingle-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to characterize aging-associated phenotypes and verify single cell sequence results.ResultsHere, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased 'senescence-associated secretory phenotype' and 'inflammation', which were major aging-associated characteristics. Further analysis of aging-related differentially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging.ConclusionTaken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type-specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility.

Dataset Information

Single-cell transcriptomic atlas of mouse cochlear aging.

Publications

Single-cell transcriptomic atlas of mouse cochlear aging.

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