Genetic module and miRNome trait analyses reflect the distinct biological features of endothelial progenitor cells from different anatomic locations

Background: Endothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair, yet EPCs from different anatomic locations possess unique biological properties. The underlying mechanisms are unclear. Method: We performed transcriptome analysis for EPCs isolated from 2 different sources: cord blood (CB) or adult peripheral blood (PB). Both gene expression microarray and small RNA sequencing (smRNA-seq) technologies were applied. Results: EPCs from CB expressed abundant genes involved in cell cycle, hypoxia signalling and blood vessel development, correlating with the phenotypes that CB-EPCs proliferated more rapidly, migrated faster, and formed tubule structure more efficiently. smRNA-seq further deciphered miRNome patterns in EPCs isolated from CB or PB: 54 miRNAs were enriched in CB-EPCs, while another 50 in PB-EPCs. Specifically, CB-EPCs expressed more angiogenic miRNAs such as miR-31, while PB-EPCs possessed more tumor suppressive miRNAs including miR-10a. Knocking down miR-31 levels in CB-EPCs suppressed cell migration and microtubule formation, while overexpressing miR-31 in PB-EPCs helped to recapitulate some of CB-EPC functions. Conclusion: Our results show the foundation for a more detailed understanding of EPCs from different anatomic sources. Stimulating the expression of angiogenic microRNAs or genes in EPCs of low activity (such as those from patients with cardiovascular diseases) might allow the development of novel therapeutic strategies. EPC from cord blood or peripheral blood that outgrown after 2-4 week culture were collected. The RNA are extracted and profiled by Affymetrix GeneChip U133 plus 2.0 expression array. This submission represents gene expression microarray component of study.

背景：内皮祖细胞（Endothelial progenitor cells, EPCs）在产后血管修复中发挥核心作用，但不同解剖部位来源的内皮祖细胞具有独特的生物学特性，其潜在机制尚未明确。
方法：本研究对分离自两种不同来源的内皮祖细胞——脐带血（cord blood, CB）与成人外周血（adult peripheral blood, PB）——开展转录组分析，同时应用了基因表达芯片与小RNA测序（small RNA sequencing, smRNA-seq）技术。
结果：脐带血来源的内皮祖细胞（CB-EPCs）高表达参与细胞周期、缺氧信号通路及血管发育的基因，这与CB-EPCs增殖更快、迁移更迅速、小管结构形成效率更高的表型相一致。小RNA测序进一步解析了两种来源内皮祖细胞的微小RNA组（miRNome）特征：54种微小RNA（miRNA）在CB-EPCs中富集，另有50种在外周血来源的内皮祖细胞（PB-EPCs）中富集。具体而言，CB-EPCs高表达促血管生成miRNA如miR-31，而PB-EPCs则高表达包括miR-10a在内的抑癌miRNA。在CB-EPCs中敲低miR-31的表达可抑制细胞迁移与微管形成，而在PB-EPCs中过表达miR-31则可重现部分CB-EPCs的功能。
结论：本研究结果为深入理解不同解剖来源的内皮祖细胞奠定了基础。激活低活性内皮祖细胞（如心血管疾病患者来源的内皮祖细胞）中的促血管生成微小RNA或基因表达，或可开发全新的治疗策略。
本研究收集经2-4周培养后扩增获得的脐带血或成人外周血来源的内皮祖细胞，提取RNA并通过Affymetrix GeneChip U133 plus 2.0表达芯片进行表达谱分析。本次提交的内容为本研究的基因表达芯片部分数据。