Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma
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Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. / Schüller, Ulrich; Heine, Vivi M; Mao, Junhao; Kho, Alvin T; Dillon, Allison K; Han, Young-Goo; Huillard, Emmanuelle; Sun, Tao; Ligon, Azra H; Qian, Ying; Ma, Qiufu; Alvarez-Buylla, Arturo; McMahon, Andrew P; Rowitch, David H; Ligon, Keith L.
in: CANCER CELL, Jahrgang 14, Nr. 2, 12.08.2008, S. 123-34.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma
AU - Schüller, Ulrich
AU - Heine, Vivi M
AU - Mao, Junhao
AU - Kho, Alvin T
AU - Dillon, Allison K
AU - Han, Young-Goo
AU - Huillard, Emmanuelle
AU - Sun, Tao
AU - Ligon, Azra H
AU - Qian, Ying
AU - Ma, Qiufu
AU - Alvarez-Buylla, Arturo
AU - McMahon, Andrew P
AU - Rowitch, David H
AU - Ligon, Keith L
PY - 2008/8/12
Y1 - 2008/8/12
N2 - 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.
AB - 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.
KW - Animals
KW - Basic Helix-Loop-Helix Transcription Factors
KW - Cell Lineage
KW - Cerebrum
KW - Crosses, Genetic
KW - Female
KW - Glial Fibrillary Acidic Protein
KW - Hedgehog Proteins
KW - Humans
KW - Male
KW - Medulloblastoma
KW - Mice
KW - Nerve Tissue Proteins
KW - Neurons
KW - Phenotype
KW - Receptors, G-Protein-Coupled
KW - Smoothened Receptor
KW - Stem Cells
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.ccr.2008.07.005
DO - 10.1016/j.ccr.2008.07.005
M3 - SCORING: Journal article
C2 - 18691547
VL - 14
SP - 123
EP - 134
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 2
ER -