肿瘤细胞治疗研究
英文原题：Early rhombic lip Protogenin(+ve) stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.
我们在四周龄人胚胎后脑中鉴定出一群Protogenin阳性（PRTG+ve）MYC高NESTIN低干细胞，其随后定位于菱脑唇的脑室区（RL VZ）。
我们在四周龄人胚胎后脑中鉴定出一群Protogenin阳性（PRTG +ve）MYC高表达NESTIN低表达的干细胞，其随后定位于菱脑唇的脑室区（RL VZ）。早期Prtg +ve菱脑唇干细胞的致癌转化可引发类似第3组髓母细胞瘤（Gr3-MB）的肿瘤。PRTG +ve干细胞在RL VZ中生长于人类特有的插入血管丛附近，这一表型在Gr3-MB中重现，但在其他类型的髓母细胞瘤中未见。Gr3-MB与内皮细胞共培养可促进肿瘤干细胞生长，同时内皮细胞呈现未成熟表型。在体内使用白喉毒素系统或CAR-T 细胞靶向Gr3-MB的PRTG高表达区室可构成有效治疗。人Gr3-MB很可能起源于早期胚胎RL VZ中居住于特定血管周围微环境的PRTG +ve干细胞。靶向PRTG高表达区室和/或血管周围微环境代表了一种治疗Gr3-MB患儿的方法。
We identify a population of Protogenin-positive (PRTG +ve ) MYC high NESTIN low stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RL VZ ). Oncogenic transformation of early Prtg +ve rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG +ve stem cells grow adjacent to a human-specific interposed vascular plexus in the RL VZ , a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTG high compartment of Gr3-MB in vivo using either the diphtheria toxin system or chimeric antigen receptor T cells constitutes effective therapy. Human Gr3-MBs likely arise from early embryonic RL VZ PRTG +ve stem cells inhabiting a specific perivascular niche. Targeting the PRTG high compartment and/or the perivascular niche represents an approach to treat children with Gr3-MB.
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