Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions

• Published in: Cell death & disease Vol. 2; no. 9; p. e200
• Main Authors: Lathia, J D, Hitomi, M, Gallagher, J, Gadani, S P, Adkins, J, Vasanji, A, Liu, L, Eyler, C E, Heddleston, J M, Wu, Q, Minhas, S, Soeda, A, Hoeppner, D J, Ravin, R, McKay, R D G, McLendon, R E, Corbeil, D, Chenn, A, Hjelmeland, A B, Park, D M, Rich, J N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-09-2011; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/1647/1407/2181; 631/67/71; 631/80/641; 692/699/67/1922; AC133 Antigen; Antibodies; Antigens, CD - analysis; Antigens, CD - metabolism; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Division; Cell Lineage; Epidermal Growth Factor - pharmacology; Fibroblast Growth Factor 2 - pharmacology; Glioma - metabolism; Glioma - pathology; Glycoproteins - analysis; Glycoproteins - metabolism; Humans; Immunology; Laminin - metabolism; Life Sciences; Mitosis; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Original; original-article; Peptides - analysis; Peptides - metabolism; cancer stem cell; asymmetric cell division; glioma
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2011.80

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.