CD41 and CD45 expression marks the angioformative initiation of neovascularisation in human haemangioblastoma
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The initiation and formation of haemangioblastoma (HB) neovascularisation remain unknown, with concomitant controversy on its cytological origin. We detected HB-derived specific haematopoietic progenitors identified by surface expression of CD41 and CD45, which are similar to human embryonic vasculogenesis. CD41/CD45 cells expressed mesodermal markers, including SCL, Flk1 and c-kit. CD41 also seemed to appear before CD45 on haematopoietic progenitors. In vitro analysis showed that the CD41+/CD45 subpopulation gave rise to occasional primitive erythroid activity and endothelial marker expression. Meanwhile, kinetic investigation of the CD41+/CD45+ subpopulation showed that some molecules, including SCL, Flk1 and c-kit, were involved in vascular formation. The CD45+/c-kit+ population that lacked primitive haematopoiesis came from CD41+ cells. Acquisition of CD45 expression by the haematopoietic progenitors was associated with advanced differentiation towards the vascular cell lineage. Taken together, the present data suggested that CD41 and CD45 expression marked the onset of HB neovascularisation and the stepwise development of the angioformative period. Our findings provide new insights into the mechanisms of HB neovascularisation and the underlying therapeutic targets of anti-vascular treatment.
KeywordsHaemangioblastomas Neovascularisation Vasculogenesis Angiogenesis Molecular characterization
This work was supported by grants from the National Natural Science Foundation of China (81172392) and the Shanghai Committee of Science and Technology (15411951800). The authors thank the Harvard Office of Technology Development of Harvard University for the human ES cell line (HuES-14) and Prof. Lei Xiao of Chinese Academy of Sciences for his technical assistance. Dr. Jingyun Yang’s research was supported by NIH/NIA R01AG036042 and the Illinois Department of Public Health.
Conflicts of interest