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前列腺六跨膜上皮抗原(STEAP1和STEAP2)——在小鼠和人间充质干细胞中差异表达。

Six-transmembrane epithelial antigen of the prostate (STEAP1 and STEAP2)-differentially expressed by murine and human mesenchymal stem cells.

作者信息

Vaghjiani Rasilaben J, Talma Sonia, Murphy Christopher L

机构信息

Faculty of Medicine, The Kennedy Institute of Rheumatology, Imperial College London, London, United Kingdom.

出版信息

Tissue Eng Part A. 2009 Aug;15(8):2073-83. doi: 10.1089/ten.tea.2008.0519.

DOI:10.1089/ten.tea.2008.0519
PMID:19196137
Abstract

Mesenchymal stem cells (MSCs) have great potential for cell-based therapies. However, lack of cell-specific markers thwarts full realization of this as it prevents their identification in vivo, and subsequent purification. In the present study, to ensure cell purity multiple individual clones were derived from the bone marrow of BALB/b and BALB/c mice, and subsequently defined as MSCs by demonstrating their multipotentiality and self-renewal ability. In an effort to define the molecular signature of such MSCs and identify potentially cell-specific markers, an extensive genome-wide microarray analysis was performed comparing eight individual undifferentiated MSC clones to four different controls-corresponding differentiated MSC clones, bone marrow adherent cells, freshly isolated bone marrow cells, and embryonic fibroblasts. Strikingly, all MSC clones expressed differentially high levels of six-transmembrane epithelial antigen of the prostate (STEAP1 and STEAP2). Further, both STEAP members showed an extremely similar expression profile to stem cell antigen-1 (Sca-1) as demonstrated by two-dimensional hierarchical cluster analysis. Most importantly, differentially high levels of STEAP1 and STEAP2 proteins were also detected in human multipotent bone marrow adherent cultures. Thus, STEAPs may represent novel markers of MSCs in man as well as mice. Depletion of STEAP1 in human MSCs using RNAi resulted in decreased cell adhesion to tissue culture plastic. Further work is now needed to fully uncover its function in these cells, and to explore its potential as a marker of MSCs.

摘要

间充质干细胞(MSCs)在基于细胞的治疗中具有巨大潜力。然而,缺乏细胞特异性标志物阻碍了其全部潜能的实现,因为这会妨碍在体内对它们的识别以及后续的纯化。在本研究中,为确保细胞纯度,从BALB/b和BALB/c小鼠的骨髓中获得了多个单独的克隆,随后通过证明它们的多能性和自我更新能力将其定义为MSCs。为了确定此类MSCs的分子特征并识别潜在的细胞特异性标志物,进行了广泛的全基因组微阵列分析,将八个未分化的单个MSC克隆与四个不同的对照——相应的分化MSC克隆、骨髓贴壁细胞、新鲜分离的骨髓细胞和胚胎成纤维细胞进行比较。令人惊讶的是,所有MSC克隆均差异高表达前列腺六跨膜上皮抗原(STEAP1和STEAP2)。此外,二维层次聚类分析表明,STEAP家族的两个成员与干细胞抗原-1(Sca-1)表现出极其相似的表达谱。最重要的是,在人多能骨髓贴壁培养物中也检测到STEAP1和STEAP2蛋白的差异高表达。因此,STEAPs可能是人和小鼠中MSCs的新型标志物。使用RNAi在人MSCs中耗尽STEAP1会导致细胞对组织培养塑料的粘附减少。现在需要进一步开展工作以全面揭示其在这些细胞中的功能,并探索其作为MSCs标志物的潜力。

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