Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma

被引：492

作者：

Schueller, Ulrich ^{[1
,5
]}

Heine, Vivi M. ^{[1
,6
,7
]}

Mao, Junhao ^{[10
]}

Kho, Alvin T. ^{[11
]}

Dillon, Allison K. ^{[1
]}

Han, Young-Goo ^{[7
]}

Huillard, Emmanuelle ^{[1
,6
,7
]}

Sun, Tao ^{[1
]}

Ligon, Azra H. ^{[3
]}

Qian, Ying ^{[4
]}

Ma, Qiufu ^{[4
]}

Alvarez-Buylla, Arturo ^{[7
,8
]}

McMahon, Andrew P. ^{[10
]}

Rowitch, David H. ^{[1
,6
,7
,8
,9
]}

Ligon, Keith L. ^{[1
,2
,3
,12
,13
]}

机构：

[1] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Cell Biol, Dana Farber Canc Inst, Boston, MA 02115 USA

[5] Univ Munich, Ctr Neuropathol & Prion Res, D-81377 Munich, Germany

[6] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA

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

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

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

[10] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA

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

[12] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA

[13] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

来源：

CANCER CELL | 2008年 / 14卷 / 02期

关键词：

D O I：

10.1016/j.ccr.2008.07.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Whether the brain tumor medulloblastoma originates from stem cells or restricted progenitor cells is unclear. To investigate this, we activated oncogenic Hedgehog (Hh) signaling in multipotent and lineage-restricted central nervous system (CNS) progenitors. We observed that normal unipotent cerebellar granule neuron precursors (CGNPs) derive from hGFAP(+) and Olig2(+) rhombic lip progenitors. Hh activation in a spectrum of early-and late-stage CNS progenitors generated similar medulloblastomas, but not other brain cancers, indicating that acquisition of CGNP identity is essential for tumorigenesis. We show in human and mouse medulloblastoma that cells expressing the glia-associated markers Gfap and Olig2 are neoplastic and retain features of embryonic-type granule lineage progenitors. Thus, oncogenic Hh signaling promotes medulloblastoma from lineage-restricted granule cell progenitors.

引用

页码：123 / 134

页数：12

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