Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015CN, the Netherlands.
Department of Orthopaedics, Erasmus MC, 3015 CE Rotterdam, the Netherlands.
Cell Rep. 2018 Jan 16;22(3):666-678. doi: 10.1016/j.celrep.2017.12.070.
Bone marrow formation requires an orchestrated interplay between osteogenesis, angiogenesis, and hematopoiesis that is thought to be mediated by endothelial cells. The nature of the endothelial cells and the molecular mechanisms underlying these events remain unclear in humans. Here, we identify a subset of endoglin-expressing endothelial cells enriched in human bone marrow during fetal ontogeny and upon regeneration after chemotherapeutic injury. Comprehensive transcriptional characterization by massive parallel RNA sequencing of these cells reveals a phenotypic and molecular similarity to murine type H endothelium and activation of angiocrine factors implicated in hematopoiesis, osteogenesis, and angiogenesis. Interleukin-33 (IL-33) was significantly overexpressed in these endothelial cells and promoted the expansion of distinct subsets of hematopoietic precursor cells, endothelial cells, as well as osteogenic differentiation. The identification and molecular characterization of these human regeneration-associated endothelial cells is thus anticipated to instruct the discovery of angiocrine factors driving bone marrow formation and recovery after injury.
骨髓的形成需要成骨作用、血管生成和造血作用之间的协调相互作用，据认为这种作用是由内皮细胞介导的。内皮细胞的性质以及这些事件背后的分子机制在人类中仍不清楚。在这里，我们鉴定了在人类胎儿发生期间和化疗损伤后再生时，富含人骨髓中的内胚层蛋白表达的内皮细胞亚群。通过大规模平行 RNA 测序对这些细胞进行全面的转录特征分析，揭示了与小鼠 H 型内皮细胞的表型和分子相似性，并激活了与造血、成骨和血管生成相关的血管分泌因子。这些内皮细胞中白细胞介素 33 (IL-33) 表达明显上调，并促进了不同造血前体细胞、内皮细胞以及成骨分化亚群的扩增。因此，这些与人类再生相关的内皮细胞的鉴定和分子特征分析有望指导发现驱动骨髓形成和损伤后恢复的血管分泌因子。
