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The cytological origin of central nervous system hemangioblastoma (HB) remains unclear and controversial, largely owing to a lack of in-depth characterization of tumorigenic cells and their progeny tracking. We have now detected a cell subpopulation by stage-specific embryonic antigen-1 expression, which were defined as tumor-initiating cells (TICs) in both sporadic and familial HBs. These TICs subpopulations had universal neural stem cell characteristics. Nevertheless, the freshly sorted TICs endowed with potential of multi-progeny derivatives, including HB components and non-HB ingredients, depended on environmental induction in vitro. Importantly, the freshly harvested TICs formed malignant tumors by injection into conventional mice model, while did redevelop the characteristic HB-like structures within a special mice model with HB-microenvironment, indicating HB niche dependency for the TICs derivative specification. Taken together, the data of the present study suggested that HBs might derive from neoplastic transformation of neural stem cells/progenitors in the specific niche. [ABSTRACT FROM PUBLISHER]