A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity.
A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity.
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DOI：
10.1038/nn.3553
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发表时间：
2013-12
影响因子：
25
通讯作者：
Yang, Zeng-jie
中科院分区：
文献类型：
--
作者：
Li, Peng;Du, Fang;Yuelling, Larra W.;Lin, Tiffany;Muradimova, Renata E.;Tricarico, Rossella;Wang, Jun;Enikolopov, Grigori;Bellacosa, Alfonso;Wechsler-Reya, Robert J.;Yang, Zeng-jie
一般认为，小脑颗粒神经元仅起源于外胚层（EGL）中的颗粒神经元前体（GNP）。在这里，我们确定了一种罕见的神经元祖细胞在小鼠小脑发育表达巢蛋白。尽管巢蛋白被广泛认为是多能干细胞的标志物，但这些表达巢蛋白的祖细胞（NEP）被定向为颗粒神经元谱系。与传统的GNP不同，GNP驻留在外部EGL中并广泛增殖，NEP驻留在EGL的深处并静止。表达谱分析揭示NEP与GNP不同，特别是与DNA修复相关的基因表达水平显著降低。与此一致，在Sonic hedgehog（Shh）信号传导的异常激活后，NEP表现出更严重的基因组不稳定性，并且比GNP更有效地产生肿瘤。这些研究确定了一种新的小脑颗粒神经元祖细胞和一种新的髓母细胞瘤起源细胞。
It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identify a rare population of neuronal progenitors in mouse developing cerebellum that expresses Nestin. Although Nestin is widely considered a marker for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are committed to the granule neuron lineage. Unlike conventional GNPs, which reside in the outer EGL and proliferate extensively, NEPs reside in the deep part of the EGL and are quiescent. Expression profiling reveals that NEPs are distinct from GNPs, and in particular, express markedly reduced levels of genes associated with DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog (Shh) signaling, NEPs exhibit more severe genomic instability and give rise to tumors more efficiently than GNPs. These studies identify a novel progenitor for cerebellar granule neurons and a novel cell of origin for medulloblastoma.
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影响因子：
64.8
作者：
BenArie, N;Bellen, HJ;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
16.2
作者：
Machold, R;Fishell, G
通讯作者：
Fishell, G
DOI：
10.1073/pnas.0601992103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Encinas, Juan M.;Vaahtokari, Anne;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori
影响因子：
16.2
作者：
MORSHEAD, CM;REYNOLDS, BA;VANDERKOOY, D
通讯作者：
VANDERKOOY, D
影响因子：
4.6
作者：
Kenney, AM;Cole, MD;Rowitch, DH
通讯作者：
Rowitch, DH