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Olig2-Regulated Lineage-Restricted Pathway Controls Replication Competence in Neural Stem Cells and Malignant Glioma

Ligon, Keith L. and Huillard, Emmanuelle and Mehta, Shwetal and Kesari, Santosh and Liu, Hongye and Alberta, John A. and Bachoo, Robert M. and Kane, Michael and Louis, David N. and DePinho, Ronald A. and Anderson, David J. and Stiles, Charles D. and Rowitch, David H. (2007) Olig2-Regulated Lineage-Restricted Pathway Controls Replication Competence in Neural Stem Cells and Malignant Glioma. Neuron, 53 (4). pp. 503-517. ISSN 0896-6273. https://resolver.caltech.edu/CaltechAUTHORS:20150305-092726096

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.neuron.2007.01.009DOIArticle
http://www.sciencedirect.com/science/article/pii/S0896627307000293PublisherArticle
ORCID:
AuthorORCID
Anderson, David J.0000-0001-6175-3872
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authors are grateful to R. Lu and L. Parada (University of Texas Southwestern) for helpful conversations and sharing unpublished data.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.
Funders:
Funding AgencyGrant Number
Robert K. Olendski American Brain Tumor AssociationUNSPECIFIED
Sontag Foundation Distinguished Scientist AwardUNSPECIFIED
Belfer Foundation for Innovative Cancer ScienceUNSPECIFIED
James S. McDonnell Research AwardUNSPECIFIED
NINDS NRSA FellowshipNS05563
NIHK08NS047213
NIHP01 CA95616
NIHPO1NS047572
NIHR01NS40511
Goldhirsh FoundationUNSPECIFIED
Issue or Number:4
Record Number:CaltechAUTHORS:20150305-092726096
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150305-092726096
Official Citation:Ligon, K. L., Huillard, E., Mehta, S., Kesari, S., Liu, H., Alberta, J. A., . . . Rowitch, D. H. (2007). Olig2-Regulated Lineage-Restricted Pathway Controls Replication Competence in Neural Stem Cells and Malignant Glioma. Neuron, 53(4), 503-517. doi: http://dx.doi.org/10.1016/j.neuron.2007.01.009
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55535
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:05 Mar 2015 18:03
Last Modified:09 Mar 2020 13:18

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