Mesenchymal progenitor cells have great therapeutic potential, yet incomplete characterization of their cell-surface interface limits their clinical exploitation. We have employed subcellular fractionation with quantitative discovery proteomics to define the cell-surface interface proteome of human bone marrow mesenchymal stromal/stem cells (MSCs) and human umbilical cord perivascular cells (HUCPVCs). We compared cell-surface-enriched fractions from MSCs and HUCPVCs (three donors each) with adult mesenchymal fibroblasts using eight-channel isobaric-tagging mass spectrometry, yielding relative quantification on >6,000 proteins with high confidence. This approach identified 186 upregulated mesenchymal progenitor biomarkers. Validation of 10 of these markers, including ROR2, EPHA2, and PLXNA2, confirmed upregulated expression in mesenchymal progenitor populations and distinct roles in progenitor cell proliferation, migration, and differentiation. Our approach has delivered a cell-surface proteome repository that now enables improved selection and characterization of human mesenchymal progenitor populations.

间充质祖细胞具有巨大的治疗潜力，但其细胞表面界面的不完整表征限制了其临床开发。我们采用亚细胞分级分离和定量发现蛋白质组学来定义人骨髓间充质基质/干细胞 (MSC) 和人脐带血管周围细胞 (HUCPVC) 的细胞表面界面蛋白质组。我们使用八通道同位素标记质谱法将来自 MSC 和 HUCPVC（各三个供体）的细胞表面富集组分与成人间充质成纤维细胞进行了比较，对 > 6,000 种蛋白质进行了相对定量，具有很高的置信度。这种方法确定了 186 个上调的间充质祖细胞生物标志物。验证这些标记中的 10 个，包括 ROR2、EPHA2 和 PLXNA2，证实了间充质祖细胞群中的上调表达以及在祖细胞增殖、迁移和分化中的不同作用。我们的方法提供了一个细胞表面蛋白质组库，现在可以改进人类间充质祖细胞群的选择和表征。