title: Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions.
abstract: Malignant gliomas contain a population of self-renewing tumorigenic stem-like cells; however, it remains unclear how these glioma stem cells (GSCs) self-renew or generate cellular diversity at the single-cell level. Asymmetric cell division is a proposed mechanism to maintain cancer stem cells, yet the modes of cell division that GSCs utilize remain undetermined. Here, we used single-cell analyses to evaluate the cell division behavior of GSCs. Lineage-tracing analysis revealed that the majority of GSCs were generated through expansive symmetric cell division and not through asymmetric cell division. The majority of differentiated progeny was generated through symmetric pro-commitment divisions under expansion conditions and in the absence of growth factors, occurred mainly through asymmetric cell divisions. Mitotic pair analysis detected asymmetric CD133 segregation and not any other GSC marker in a fraction of mitoses, some of which were associated with Numb asymmetry. Under growth factor withdrawal conditions, the proportion of asymmetric CD133 divisions increased, congruent with the increase in asymmetric cell divisions observed in the lineage-tracing studies. Using single-cell-based observation, we provide definitive evidence that GSCs are capable of different modes of cell division and that the generation of cellular diversity occurs mainly through symmetric cell division, not through asymmetric cell division.
authors: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. lathiaj@ccf.org
authors: J D
authors: JD
authors: Lathia
authors: M
authors: M
authors: Hitomi
authors: J
authors: J
authors: Gallagher
authors: S P
authors: SP
authors: Gadani
authors: J
authors: J
authors: Adkins
authors: A
authors: A
authors: Vasanji
authors: L
authors: L
authors: Liu
authors: C E
authors: CE
authors: Eyler
authors: J M
authors: JM
authors: Heddleston
authors: Q
authors: Q
authors: Wu
authors: S
authors: S
authors: Minhas
authors: A
authors: A
authors: Soeda
authors: D J
authors: DJ
authors: Hoeppner
authors: R
authors: R
authors: Ravin
authors: R D G
authors: RD
authors: McKay
authors: R E
authors: RE
authors: McLendon
authors: D
authors: D
authors: Corbeil
authors: A
authors: A
authors: Chenn
authors: A B
authors: AB
authors: Hjelmeland
authors: D M
authors: DM
authors: Park
authors: J N
authors: JN
authors: Rich
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D002455:Cell Division; D019070:Cell Lineage; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008938:Mitosis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000032:analysis / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D007797:Laminin; C000606023:PROM1 protein, human; D010455:Peptides; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor