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来自器官型外植体的年轻和成熟血管纹之间的分子差异与转录组学

Molecular differences between young and mature stria vascularis from organotypic explants and transcriptomics.

作者信息

Thulasiram Matsya Ruppari, Yamamoto Ryosuke, Olszewski Rafal T, Gu Shoujun, Morell Robert J, Hoa Michael, Dabdoub Alain

机构信息

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre Toronto, ON M4N 3M5, Canada.

出版信息

iScience. 2025 Jan 17;28(2):111832. doi: 10.1016/j.isci.2025.111832. eCollection 2025 Feb 21.

Abstract

The stria vascularis (SV) is an essential component of the inner ear that regulates the ionic environment required for hearing. SV degeneration disrupts cochlear homeostasis, leading to irreversible hearing loss, yet a comprehensive understanding of the SV, and consequently therapeutic availability for SV degeneration, is lacking. We developed a whole-tissue explant model from neonatal and mature mice to create a platform for advancing SV research. We validated our model by demonstrating that the proliferative behavior of the SV mimics SV . We also provided evidence for pharmacological experimentation by investigating the role of Wnt/β-catenin signaling in SV proliferation. Finally, we performed single-cell RNA sequencing from neonatal and mature mouse SV and surrounding tissue and revealed key genes and pathways that may play a role in SV proliferation and maintenance. Together, our results contribute new insights into investigating biological solutions for SV-associated hearing loss.

摘要

血管纹(SV)是内耳的一个重要组成部分,它调节听力所需的离子环境。SV变性会破坏耳蜗内环境稳定,导致不可逆的听力损失,但目前缺乏对SV的全面了解,因此也缺乏针对SV变性的治疗方法。我们从新生小鼠和成年小鼠中开发了一种全组织外植体模型,以创建一个推进SV研究的平台。我们通过证明SV的增殖行为模拟了SV来验证我们的模型。我们还通过研究Wnt/β-连环蛋白信号在SV增殖中的作用,为药理学实验提供了证据。最后,我们对新生小鼠和成年小鼠的SV及周围组织进行了单细胞RNA测序,揭示了可能在SV增殖和维持中起作用的关键基因和途径。总之,我们的结果为研究与SV相关的听力损失的生物学解决方案提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d4c/11869990/a5ab9472c31e/fx1.jpg

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