title: Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma.
abstract: Within high-grade gliomas, the precise identities and functional roles of stem-like cells remain unclear. In the normal neurogenic niche, ID (Inhibitor of DNA-binding) genes maintain self-renewal and multipotency of adult neural stem cells. Using PDGF- and KRAS-driven murine models of gliomagenesis, we show that high Id1 expression (Id1(high)) identifies tumor cells with high self-renewal capacity, while low Id1 expression (Id1(low)) identifies tumor cells with proliferative potential but limited self-renewal capacity. Surprisingly, Id1(low) cells generate tumors more rapidly and with higher penetrance than Id1(high) cells. Further, eliminating tumor cell self-renewal through deletion of Id1 has modest effects on animal survival, while knockdown of Olig2 within Id1(low) cells has a significant survival benefit, underscoring the importance of non-self-renewing lineages in disease progression.
authors.affiliation: Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Lindy E
authors.initials: LE
authors.lastname: Barrett
authors.forename: Zvi
authors.initials: Z
authors.lastname: Granot
authors.forename: Courtney
authors.initials: C
authors.lastname: Coker
authors.forename: Antonio
authors.initials: A
authors.lastname: Iavarone
authors.forename: Dolores
authors.initials: D
authors.lastname: Hambardzumyan
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
authors.forename: Hyung-song
authors.initials: HS
authors.lastname: Nam
authors.forename: Robert
authors.initials: R
authors.lastname: Benezra
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D051798:Inhibitor of Differentiation Protein 1; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C497455:Idb1 protein, mouse; C512773:Olig2 protein, mouse