Olig2-Regulated Lineage-Restricted Pathway Controls Replication Competence in Neural Stem Cells and Malignant Glioma
Abstract
Recent studies have identified stem cells in brain cancer. However, their relationship to normal CNS progenitors, including dependence on common lineage-restricted pathways, is unclear. We observe expression of the CNS-restricted transcription factor, OLIG2, in human glioma stem and progenitor cells reminiscent of type C transit-amplifying cells in germinal zones of the adult brain. Olig2 function is required for proliferation of neural progenitors and for glioma formation in a genetically relevant murine model. Moreover, we show p21^(WAF1/CIP1), a tumor suppressor and inhibitor of stem cell proliferation, is directly repressed by OLIG2 in neural progenitors and gliomas. Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells.
Additional Information
© 2007 Elsevier B.V. Received: September 25, 2006; Revised: December 11, 2006; Accepted: January 10, 2007; Published: February 14, 2007. The authors are grateful to R. Lu and L. Parada (University of Texas Southwestern) for helpful conversations and sharing unpublished data. The authors wish to thank Dong-in Yuk, Emily Learner, and Emily Jerczyk for expert technical assistance. E.H. is the recipient of a Robert K. Olendski American Brain Tumor Association fellowship. S.K. is supported by a Sontag Foundation Distinguished Scientist Award. R.A.D. is an American Cancer Society Research Professor and an Ellison Medical Foundation Senior Scholar and is supported by the Belfer Foundation for Innovative Cancer Science. D.J.A. is a HHMI Investigator, and D.H.R. is recipient of a James S. McDonnell Research Award. S.M. is the recipient of an NRSA fellowship NS05563 from NINDS. This work was supported by grants from the NIH to K.L.L. (K08NS047213), R.A.D. (P01 CA95616), C.D.S. (PO1NS047572), and D.H.R. (R01NS40511) and by a grant from the Goldhirsh Foundation, Boston, MA, to C.D.S.Attached Files
Supplemental Material - mmc1.pdf
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Additional details
- Eprint ID
- 55535
- Resolver ID
- CaltechAUTHORS:20150305-092726096
- Robert K. Olendski American Brain Tumor Association
- Sontag Foundation Distinguished Scientist Award
- Belfer Foundation for Innovative Cancer Science
- James S. McDonnell Research Award
- NS05563
- NINDS NRSA Fellowship
- K08NS047213
- NIH
- P01 CA95616
- NIH
- PO1NS047572
- NIH
- R01NS40511
- NIH
- Goldhirsh Foundation
- Created
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2015-03-05Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field