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Li P , Du F , Yuelling LW , Lin T , Muradimova RE , Tricarico R , Wang J , Enikolopov G , Bellacosa A , Wechsler-Reya RJ , Yang ZJ
A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity
Nat Neurosci. 2013 Dec;16(12) :1737-44
PMID: 24141309    PMCID: PMC3845444    URL: https://www.ncbi.nlm.nih.gov/pubmed/24141309
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It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identified 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 revealed 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 exhibited more severe genomic instability and gave rise to tumors more efficiently than GNPs. These studies revealed a previously unidentified progenitor for cerebellar granule neurons and a cell of origin for medulloblastoma.
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 eng 5T32CA009035-37/CA/NCI NIH HHS/ U19-AI067798/AI/NIAID NIH HHS/ R01-CA178380/CA/NCI NIH HHS/ R01-CA122759/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Nat Neurosci. 2013 Dec;16(12):1737-44. doi: 10.1038/nn.3553. Epub 2013 Oct 20.