转录谱揭示内皮细胞(PEC)与成人循环EPCs的iPS-derived祖细胞的根本差异
Transcriptional profiling reveals fundamental differences in iPS-derived progenitors of endothelial cells (PECs) versus adult circulating EPCs
摘要:
有许多不同的干细胞来源,有可能被用作血管退行性疾病的治疗剂。一方面,存在所谓的内皮祖细胞(EPC),其通常来源于成人血液。它们携带标志物CD34,但EPCs的真正性质和定义仍然存在争议。另一方面,存在内皮细胞(PEC)的胚胎前体,其也表达CD34,并且可以在体外从胚胎干细胞(ESC)或诱导多能干细胞(iPSC)分化。本研究旨在通过全基因组转录谱(RNAseq)比较这两种不同的CD34阳性细胞群。为此,我们首先优化了PEC分化方案,并发现血管内皮生长因子(VEGF)对于细胞从中胚层前体向PEC的转变至关重要。此外,RNAseq数据的主成分分析(PCA)显示,血液来源的EPC远离iPS来源的PEC聚类,这说明这些群体是根本不同的。这些数据将有助于更好地定义这些细胞群,促进该领域再生方法的转化,并提供潜在的新型诊断工具。
英文摘要:
There are a number of different stem cell sources that have the potential to be used as therapeutics in vascular degenerative diseases. On the one hand, there are so called endothelial progenitor cells (EPCs), which are typically derived from adult blood. They carry the marker CD34, but the true nature and definition of EPCs is still controversial. On the other hand, there are embryonic precursors of endothelial cells (PECs), which also express CD34, and can be differentiated from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in vitro. In this study, it was aimed to compare these two different CD34 positive cell populations by full genome transcriptional profiling (RNAseq). To this end, we firstly optimised a PEC differentiation protocol and found that vascular endothelial growth factor (VEGF) is critical for the transition of cells from mesodermal precursors to PECs. Additionally, principal component analysis (PCA) of RNAseq data showed that blood-derived EPCs clustered far from iPS-derived PECs which illustrates these populations are fundamentally different. This data will be useful to better define these cell populations and facilitating the translation of regenerative approaches in this field as well as providing potentially novel diagnostic tools.
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