Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma

被引：417

作者：

Ligon, Keith L.

Huillard, Emmanuelle

Mehta, Shwetal

Kesari, Santosh

Liu, Hongye

Alberta, John A.

Bachoo, Robert M.

Kane, Michael

Louis, David N.

DePinho, Ronald A.

Anderson, David J.

Stiles, Charles D.

Rowitch, David H.

机构：

[1] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA

[6] Childrens Hosp, Informat Program, Boston, MA 02115 USA

[7] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA

[8] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02129 USA

[9] CALTECH, Howard Hughes Med Inst, Div Biol, Pasadena, CA 91125 USA

[10] Childrens Hosp, Div Neonatol, Boston, MA 02115 USA

[11] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

[12] Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA

[13] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

[14] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA

[15] Univ Calif San Francisco, Inst Regenerat Med, San Francisco, CA 94143 USA

来源：

NEURON | 2007年 / 53卷 / 04期

关键词：

D O I：

10.1016/j.neuron.2007.01.009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：503 / 517

页数：15

共 83 条

[1] Negative control elements of the cell cycle in human tumors [J].