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Tissue-Specific Stem Cells
Article first published online: 19 DEC 2012
Copyright © 2012 AlphaMed Press
Volume 31, Issue 1, pages 190–202, January 2013
How to Cite
Acquati, S., Greco, A., Licastro, D., Bhagat, H., Ceric, D., Rossini, Z., Grieve, J., Shaked-Rabi, M., Henriquez, N. V., Brandner, S., Stupka, E. and Marino, S. (2013), Epigenetic Regulation of Survivin by Bmi1 Is Cell Type Specific During Corticogenesis and in Gliomas. STEM CELLS, 31: 190–202. doi: 10.1002/stem.1274
Author contributions: S.A. and A.G.: collection and/or assembly of data, data analysis and interpretation, and manuscript writing; D.L. and E.S.: data analysis and interpretation; H.B., D.C., and Z.R.: collection and/or assembly of data; J.G. and M.S.-R.: provision of study material or patients; N.V.H. and S.B.: provision of study material or patients and data analysis and interpretation; S.M.: conception and design, data analysis and interpretation, financial support, and manuscript writing. S.A. and A.G. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 6, 2012.
- Issue published online: 19 DEC 2012
- Article first published online: 19 DEC 2012
- Accepted manuscript online: 6 NOV 2012 11:34PM EST
- Manuscript Accepted: 17 SEP 2012
- Manuscript Received: 2 APR 2012
- Medical Research Council U.K.. Grant Numbers: G0800020, 85704
- Cancer Research Fund. Grant Number: 442/1289
- National Hospital Development Foundation, UCL ION
- NIHR Comprehensive Biomedical Research Centre. Grant Number: CBRC 31
- Samantha Dickson Brain Tumor Trust. Grant Number: SDBTT 0805
- Oxidative stress;
- DNA damage;
- Neural stem cells;
Polycomb group proteins are essential regulators of stem cell function during embryonic development and in adult tissue homeostasis. Bmi1, a key component of the Polycomb Repressive Complex 1, is highly expressed in undifferentiated neural stem cells (NSC) as well as in several human cancers including high-grade gliomas—highly aggressive brain tumors. Using a conditional gene activation approach in mice, we show that overexpression of Bmi1 induces repressive epigenetic regulation of the promoter of Survivin, a well-characterized antiapoptotic protein. This phenomenon is cell type-specific and it leads to apoptotic death of progenitor cells exclusively upon commitment toward a neuronal fate. Moreover, we show that this is triggered by increased oxidative stress-induced DNA damage. In contrast, undifferentiated NSC as well as glioma-initiating cells display an open chromatin configuration at the Survivin promoter and do not undergo apoptotic death. These findings raise the possibility that normal and neoplastic stem cells depend on the same mechanism for surviving the hyperproliferative state induced by increased Bmi1 expression. STEM Cells2013;31:190–202