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Acquisition of Granule Neuron Precursor Identity Is a Critical Determinant of Progenitor Cell Competence to Form Shh-Induced Medulloblastoma
Cancer Cell, Issue: 2, Volume: 14, Pages: 123-134. | 2008-01-08
0 Patent citations    252 Scholarly citations     Reference Count: 59
Ulrich Schuller;Vivi M Heine;Junhao Mao;Alvin T Kho;Allison K Dillon;Young-Goo Han;Emmanuelle Huillard;Tao Sun;Azra H Ligon;Ying Qian;Qiufu Ma;Arturo Alvarez-Buylla;Andrew P McMahon;David H Rowitch;Keith L Ligon

摘要

Summary 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.


机构

Harvard University;Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.Harvard UniversityHarvard UniversityBoston Children's HospitalHarvard UniversityUniversity of California, San FranciscoHarvard UniversityHarvard UniversityHarvard UniversityHarvard UniversityHarvard UniversityUniversity of California, San FranciscoHarvard UniversityHarvard UniversityHarvard University


文献类型:

journal article;research support, n.i.h., extramural;research support, non-u.s. gov't;

出版商:

Cell Press

发表时间:

2008-01-08

基金信息

NINDS NIH HHS(K08 NS047213)United States