首页|再生障碍性贫血骨髓微环境脂肪化相关lncRNA的筛选与鉴定

再生障碍性贫血骨髓微环境脂肪化相关lncRNA的筛选与鉴定

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目的:系统筛选与鉴定再生障碍性贫血(再障,AA)骨髓微环境脂肪化相关的长非编码RNA(lncRNA).方法:通过生物信息学分析ChIPBase中PPARγ和C/EBPα的ChIP-Seq数据,筛选PPARγ和C/EBPα共转录调控的候选lncRNA,并在骨髓间充质干细胞(BM-MSC)的体外成脂分化模型、敲低PPARγ和C/EBPα表达的BM-MSC以及临床再障BM-MSC样本中通过qRT-PCR验证候选lncRNA的表达.结果:qRT-PCR检测结果显示,成脂分化转录因子PPARγ和C/EBPα在再障来源BM-MSC中均显著高表达,敲低二者表达可以显著抑制再障BM-MSC的成脂分化能力;PPARγ和C/EBPα以结合位点依赖性的方式转录调控LINC01230启动子活性;与对照相比,LINC01230在再障BM-MSC中异常高表达.结论:PPARγ和C/EBPα在再障BM-MSC中异常表达,可能通过转录激活LINC01230促进再障BM-MSC成脂分化,并在一定程度上介导再障骨髓微环境脂肪化的发生.
Screening and Identification of lncRNA Related to Adipocity of Bone Marrow Microenvironment in Aplastic Anemia
Objective:To systematically screen and identify long noncoding RNA(lncRNA)associated with bone marrow adiposity changes in aplastic anemia(AA).Methods:The PPARγ and C/EBPα ChIP-Seq data in ChIPBase was analyzed by bioinformatics and the potential lncRNA co-transcriptionally regulated by PPARγ and C/EBPα was screened.The expression of candidate lncRNA was verified by qRT-PCR in the in vitro adipogenic differentiation model of BM-MSC,BM-MSC infected with lenti-shPPARγ and lenti-shC/EBPα as well as clinical BM-MSC samples derived from AA and controls.Results:PPARγ and C/EBPα were significantly highly expressed in AA BM-MSC,and knock-down of PPARγ and C/EBPα impaired the adipogenic capacity of AA BM-MSC.PPARγ and C/EBPα cotranscriptionally activate LINC01230 promoter activity in binding sites dependant manner.The LINC01230 was also aberrantly highly expressed in AA BM-MSC compared with controls.Conclusion:PPARγ and C/EBPα are aberrantly expressed in AA BM-MSC and may promote the adipogenic differentiation of AA BM-MSC,and to a certain extent mediate the bone marrow adiposity alteration by transcriptionally activating LINC01230 expression.

aplastic anemiabone marrow mesenchymal stem cellPPARγC/EBPαlong noncoding RNA

刘磊、张环环、张现宁、刘路路、陈明台

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济宁医学院附属医院血液科,山东济宁 272000

济宁医学院附属医院手术室,山东济宁 272000

济宁医学院附属医院医学研究中心,山东济宁 272000

再生障碍性贫血 骨髓间充质干细胞 PPARγ C/EBPα 长非编码RNA

山东省自然科学基金山东省"泰山学者"项目山东省高等学校"青创团队"计划济宁医学院附属医院博士启动基金

ZR2022MH108tsqn2022113672022KJ1052021-BS-012

2024

中国实验血液学杂志
中国病理生理学会

中国实验血液学杂志

CSTPCD北大核心
影响因子:0.988
ISSN:1009-2137
年,卷(期):2024.32(2)
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