Early B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

早期 B 细胞因子-1 (EBF1) 是一种转录因子，在细胞成熟的早期阶段在细胞谱系规范和定型中具有重要作用。EBF1 最初在 B 细胞成熟过程中被描述，随后被鉴定为间充质干细胞向脂肪细胞、成骨细胞和肌肉细胞的正确细胞命运承诺的关键分子。在血管中，从未记录过 EBF1 的表达和功能。我们的数据表明，EBF1 在肿瘤血管和生理条件下的内皮周围细胞中高度表达。免疫组织化学、定量逆转录聚合酶链反应 (RT-qPCR) 和荧光激活细胞分选 (FACS) 分析表明，表达 EBF1 的内皮周围细胞是真正的周细胞并选择性表达用于鉴定周细胞表型的公认标记（SMA、PDGFRβ、CD146、NG2）。这一观察结果也在体外人胎盘衍生的周细胞和人脑血管周细胞 (HBVP) 中得到证实。值得注意的是，根据 EBF1 在间充质干细胞的细胞谱系定型中的关键作用，EBF1 沉默的 HBVP 细胞显示 PDGFRβ 和 CD146 显着降低，但 CD90 没有显着降低，CD90 是主要与显着的间充质表型相关的标志物。此外，血管生成过程中由周细胞产生并与其分化和活化相关的细胞因子 VEGF、血管生成素-1、NG2 和 TGF-β 的表达水平也显着降低。总体而言，数据表明 EBF1 在细胞命运对周细胞表型的承诺中的功能性作用。