A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity

Li, P., Du, F., Yuelling, L. W., Lin, T., Muradimova, R. E., Tricarico, R., Wang, J., Enikolopov, G., Bellacosa, A., Wechsler-Reya, R. J., Yang, Z. J (October 2013) A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity. Nature Neuroscience. ISSN 10976256 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/24141309

DOI: 10.1038/nn.3553

Abstract

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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > tissues types and functions > cerebellum bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > nestin organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Enikolopov, Grigori N.
Communities:	CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Microscopy Service CSHL labs > Enikopolov lab CSHL Cancer Center Program > Signal Transduction
Depositing User:	Matt Covey
Date:	October 2013
Date Deposited:	11 Nov 2013 21:12
Last Modified:	19 Jul 2021 14:14
PMCID:	PMC3845444
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/28858

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