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缺氧对人软骨终板来源干细胞的一般调节作用:差异基因表达和可变剪接事件的全基因组分析

General regulatory effects of hypoxia on human cartilage endplate‑derived stem cells: A genome‑wide analysis of differential gene expression and alternative splicing events.

作者信息

Yao Yuan, Song Weilin, Deng Qiyue, Zhang Huiyu, Wang Jian, Liu Huan, Zhou Yue

机构信息

Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.

Department of Ophthalmology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.

出版信息

Mol Med Rep. 2017 Sep;16(3):3001-3009. doi: 10.3892/mmr.2017.6907. Epub 2017 Jun 30.

Abstract

Intervertebral disc (IVD) degeneration of is considered to be initiated by the degeneration of the cartilage endplate (CEP). CEP‑derived stem cells (CESCs) with the capacity for osteochondrogenic differentiation may be responsible for CEP cartilage restoration. As CEP is avascular and hypoxic, and hypoxia can greatly influence biological activities of stem cells, physiological hypoxia may serve important roles in regulating the physiological functions of CESCs. The aim of the present study was to investigate the mechanisms of hypoxia‑regulated CESCs fate by using the Human Transcriptome Array 2.0 system to identify differentially expressed genes (DEGs) and alternatively spliced genes (ASGs) in CESCs cultured under hypoxic and normoxic conditions. The high‑throughput analysis of both DEGs and ASGs were notably enriched in the immune response signal, which so far has not been investigated in IVD cells, due to their avascular nature and low immunogenicity. The present results provided a referential study direction of the mechanisms of hypoxia‑regulated CESC fate at the level of gene expression and alternative splicing, which may aid in our understanding of the processes of CEP degeneration.

摘要

椎间盘(IVD)退变被认为是由软骨终板(CEP)退变引发的。具有成骨软骨分化能力的CEP来源干细胞(CESCs)可能负责CEP软骨修复。由于CEP无血管且缺氧,而缺氧可极大影响干细胞的生物学活性,生理性缺氧可能在调节CESCs的生理功能中发挥重要作用。本研究的目的是通过使用人类转录组阵列2.0系统来鉴定在缺氧和常氧条件下培养的CESCs中的差异表达基因(DEGs)和可变剪接基因(ASGs),从而研究缺氧调节CESCs命运的机制。DEGs和ASGs的高通量分析在免疫反应信号中显著富集,由于IVD细胞无血管且免疫原性低,迄今为止尚未在IVD细胞中对此进行研究。本研究结果在基因表达和可变剪接水平上为缺氧调节CESCs命运的机制提供了一个参考研究方向,这可能有助于我们理解CEP退变的过程。

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