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.
题目: 再生障碍性贫血骨髓微环境脂肪化相关lncRNA的筛选与鉴定.
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。.
Keywords: aplastic anemia; bone marrow mesenchymal stem cell; PPARγ; C/EBPα; long noncoding RNA.