title: A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity.
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.
authors.affiliation: 1] Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania, USA. [2] Department of Clinical Biochemistry, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.forename: Larra W
authors.initials: LW
authors.lastname: Yuelling
authors.forename: Tiffany
authors.initials: T
authors.lastname: Lin
authors.forename: Renata E
authors.initials: RE
authors.lastname: Muradimova
authors.forename: Rossella
authors.initials: R
authors.lastname: Tricarico
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Grigori
authors.initials: G
authors.lastname: Enikolopov
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bellacosa
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wechsler-Reya
authors.forename: Zeng-jie
authors.initials: ZJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D000072079:Patched Receptors; D011956:Receptors, Cell Surface / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D051792:Basic Helix-Loop-Helix Proteins; D008164:Luminescent Proteins; D064231:Nestin; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D013629:Tamoxifen; C500943:Atoh1 protein, mouse; C577485:Nes protein, mouse; C413663:fluorescent protein 583