人骨髓间充质干细胞诱导分化为汗腺样细胞过程中microRNA表达谱差异的分析  

Analysis on differential expression profiles of microRNA in the process of human bone marrow mesenchymal stem cells differentiated into sweat gland-like cells

作　　者：陈艳[1,2] 赵洪良[3] 谭志军[3] 赵焕军[3] 张翠萍[3] 付小兵[2,3] 

机构地区：[1]北京军区总医院药理科,北京100700 [2]解放军总医院基础医学研究所,北京100853 [3]解放军总医院第一附属医院全军创伤修复与组织再生重点实验室暨皮肤损伤修复与组织再生北京市重点实验室,北京100048

出　　处：《感染．炎症．修复》2016年第1期6-11,共6页Infection Inflammation Repair

基　　金：国家"973"计划资助项目(2012CB518105);国家自然科学基金项目(81121004;81230041;81171798)

摘　　要：目的:利用微小RNA(microRNA)表达谱基因芯片检测新技术,寻找人骨髓间充质干细胞(MSCs)分化为汗腺样细胞(SGLCs)过程中的关键microRNAs及其介导的分子信号通路。方法:通过间接培养方法诱导MSCs分化为SGLCs后,利用microRNA基因芯片检测,分析MSCs诱导前后以及MSCs、SGLC与正常成人汗腺细胞(SGCs)之间microRNA差异表达谱,筛选出其中发生极其显著改变的microRNAs,通过microRNA靶点预测软件,进一步筛选出其中直接靶向与汗腺发育、干细胞分化相关基因的microRNAs及其靶基因。结果:microRNA表达谱的差异比对结果显示,SGLCs与MSCs相比,19个microRNAs上调,49个microRNAs下调;SGCs与MSCs相比,120个microRNAs上调,59个microRNAs下调。取SGLCs与MSCs差异表达谱和SGCs与MSCs差异表达谱的交集,发现37个microRNAs在以上两个差异表达谱中均出现,其中12个microRNAs上调,25个microRNAs下调,它们可直接靶向与汗腺发育和干细胞分化相关的CEA等多个细胞因子,并参与EDA/EDAR、NF-κB、Wnt、ERK等多个相关信号通路的调节。结论:通过生物信息学靶点分析,成功寻找到在MSCs分化为SGLCs的过程中,靶向汗腺发育和干细胞分化相关细胞因子和信号通路的关键microRNAs。Objective To search the key microRNAs and investigate the microRNA-mediated regulating mechanismson molecular signaling pathways by microRNA expressing profile gene chips detection in the process of human bonemarrow mesenchymal stem cells （MSCs） differentiated into sweat gland-like cells （SGLCs）. Methods： MSCs was inducedto differentiate into SGLCs by the method of indirect culture. The profiles of microRNA differential expression in MSCsbefore and after differentiation, as well as in MSCs, SGLCs and adult matured sweat gland cells （SGCs） were arrayed bymicroRNA microarray detection, the markedly changed microRNAs were screened out. Subsequently, the significantlychanged microRNAs which targeted the genes related to SGCs development and MSCs differentiation were screened outby microRNA target prediction software for further validation. Results： The comparison results of microRNA differentialexpression profiles showed that 19 microRNAs were up-regulated and 49 microRNAs down-regulated in SGLCs vs. MSCs.While 120 microRNAs up-regulated and 59 microRNAs down-regulated in SGCs vs. MSCs. Thirty-seven microRNAs werefound simultaneously in the result of significantly changed microRNAs in SGLCs vs. MSCs and SGCs vs. MSCs, in which12 up-regulated and 25 down-regulated. All the 37 microRNAs targeted directly to a number of cytokines related to the sweat gland development and stem cells differentiation like CEA, and participated in the regulation of signaling pathways of EDA/EDAR, NF-κB, Wnt and ERK, etc. Conclusions： A series of differentially expressed microRNAs targeting to related cytokines and signaling pathways correlated with regulation of SGCs development and differentiation of MSCs have been found successfully by bioinformatics analysis..

关 键 词：骨髓间充质干细胞 汗腺细胞 MICRORNA表达谱 差异性分析 

分 类 号：R394[医药卫生—医学遗传学]