title: Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human medulloblastoma molecular classification.
abstract: Medulloblastoma arises from mutations occurring in stem/progenitor cells located in restricted hindbrain territories. Here we report that the mouse postnatal ventricular zone lining the IV ventricle also harbors bona fide stem cells that, remarkably, share the same molecular profile with cerebellar white matter-derived neural stem cells (NSC). To identify novel molecular mediators involved in medulloblastomagenesis, we compared these distinct postnatal hindbrain-derived NSC populations, which are potentially tumor initiating, with murine compound Ptch/p53 mutant medulloblastoma cancer stem cells (CSC) that faithfully phenocopy the different variants of human medulloblastoma in vivo. Transcriptome analysis of both hindbrain NSCs and medulloblastoma CSCs resulted in the generation of well-defined gene signatures, each reminiscent of a specific human medulloblastoma molecular subclass. Most interestingly, medulloblastoma CSCs upregulated developmentally related genes, such as Ebfs, that were shown to be highly expressed in human medulloblastomas and play a pivotal role in experimental medullo-blastomagenesis. These data indicate that gene expression analysis of medulloblastoma CSCs holds great promise not only for understanding functional differences between distinct CSC populations but also for identifying meaningful signatures that might stratify medulloblastoma patients beyond histopathologic staging.
authors.affiliation: Neural Stem Cell Biology Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientifi c Institute, Via Olgettina 58, 20132 Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Corno
authors.forename: Corno
authors.initials: C
authors.lastname: Daniela
authors.forename: Mauro
authors.initials: M
authors.lastname: Pala
authors.forename: Manuela
authors.initials: M
authors.lastname: Cominelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Cipelletti
authors.forename: Ketty
authors.initials: K
authors.lastname: Leto
authors.forename: Laura
authors.initials: L
authors.lastname: Croci
authors.forename: Valeria
authors.initials: V
authors.lastname: Barili
authors.forename: Federico
authors.initials: F
authors.lastname: Brandalise
authors.forename: Raffaella
authors.initials: R
authors.lastname: Melzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Gregorio
authors.forename: Lucia Sergi
authors.initials: LS
authors.lastname: Sergi
authors.forename: Letterio Salvatore
authors.initials: LS
authors.lastname: Politi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bulfone
authors.forename: Paola
authors.initials: P
authors.lastname: Rossi
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
authors.forename: Gian Giacomo
authors.initials: GG
authors.lastname: Consalez
authors.forename: Pietro Luigi
authors.initials: PL
authors.lastname: Poliani
authors.forename: Rossella
authors.initials: R
authors.lastname: Galli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002528:Cerebellar Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D008527:Medulloblastoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology