Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes
Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes
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DOI：
10.1038/onc.2010.609
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发表时间：
2011-05-01
期刊：
影响因子：
8
通讯作者：
Giovannini, M.
中科院分区：
文献类型：
--
作者：
Kalamarides, M.;Stemmer-Rachamimov, A. O.;Giovannini, M.
脑膜瘤是成人最常见的原发性中枢神经系统肿瘤之一。由于缺乏关于这些脑肿瘤起源细胞的信息，集中于脑膜瘤发展的分子基础的研究受到阻碍。在此，我们确定了前列腺素D合成酶阳性脑膜前体细胞作为小鼠脑膜瘤的起源细胞，并表明在三层脑膜形成之前，前列腺素D2合成酶（PGDS）（+）原始脑膜细胞中的神经纤维瘤病2型（Nf 2）失活，解释了脑膜瘤组织学亚型的异质性。使用一种独特的PGDSCre株，我们定义了一个关键的胚胎和出生后早期发育窗口，其中PGDS（+）祖细胞中的双等位基因Nf 2失活导致脑膜瘤形成。此外，我们确定了差异表达的标志物，表征两个主要的组织学脑膜瘤亚型在人类和小鼠肿瘤。总的来说，这些发现确立了这些常见脑肿瘤的起源细胞，以及一个敏感的发育期，在该发育期，标志性基因突变最终导致脑膜瘤形成。Oncogene（2011）30，2333-2344; doi：10.1038/onc.2010.609; 2011年1月17日在线发表
Meningiomas are among the most common primary central nervous system tumours in adults. Studies focused on the molecular basis for meningioma development are hampered by a lack of information with regard to the cell of origin for these brain tumours. Herein, we identify a prostaglandin D synthase-positive meningeal precursor as the cell of origin for murine meningioma, and show that neurofibromatosis type 2 (Nf2) inactivation in prostaglandin D2 synthase (PGDS) (+) primordial meningeal cells, before the formation of the three meningeal layers, accounts for the heterogeneity of meningioma histological subtypes. Using a unique PGDSCre strain, we define a critical embryonic and early postnatal developmental window in which biallelic Nf2 inactivation in PGDS (+) progenitor cells results in meningioma formation. Moreover, we identify differentially expressed markers that characterize the two major histological meningioma subtypes both in human and mouse tumours. Collectively, these findings establish the cell of origin for these common brain tumours as well as a susceptible developmental period in which signature genetic mutations culminate in meningioma formation. Oncogene (2011) 30, 2333-2344; doi: 10.1038/onc.2010.609; published online 17 January 2011