Quantitative analysis of mitotic Olig2 cells in adult human brain and gliomas: implications for glioma histogenesis and biology.
The capacity of adult human glial progenitor cells (AGPs), to proliferate and undergo multipotent differentiation, positions them as ideal candidate cells of origin for human gliomas. To investigate this potential role we identified AGPs as mitotically active Olig2 cells in nonneoplastic adult human brain and gliomas. We conservatively estimated that one in 5,000 human temporal lobe neocortical gray or subcortical white matter cells is mitotic. Extrapolating from a mean Olig2/Mib-1 labeling index (LI) of 52% and total cell number of 100 billion, we estimated the overall prevalence of mitotic Olig2 AGPs in nonneoplastic human brain parenchyma at 10 million. These data identify a large reservoir of Olig2 AGPs which could be potential targets for human gliomagenesis. The vast majority of mitotic cells in Grade II and Grade III gliomas of all histologic subtypes expressed Olig2 (mean LI 75%) but rarely S100B (LI 0.6%), identifying the Olig2 cell as a distinct contributor to the proliferating cell population of human gliomas of both oligodendroglial and astrocytic lineages. In the most malignant Grade IV glioma, or glioblastoma multiforme (GBM), the prevalence of Olig2/Mib-1 cells was significantly decreased (24.5%). The significantly lower Olig2/Mib-1 LI in GBMs suggests that a decrease in the prevalence of Olig2 cells to the total mitotic cell pool accompanies increasing malignancy. The novel framework provided by this quantitative and comparative analysis supports future studies to examine the histogenetic role of Olig2 AGPs in adult gliomas, their potential contribution to the tumor stroma and the molecular role of Olig2 in glioma pathogenesis.
Department of Neurological Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle,WA 98195-6470, USA.
Wootack
W
Rhee
Sutapa
S
Ray
Hideaki
H
Yokoo
Megan E
ME
Hoane
Chong C
CC
Lee
Andrei M
AM
Mikheev
Philip J
PJ
Horner
Robert C
RC
Rostomily
D000293:Adolescent; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology*; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis*; D001921:Brain / Q000166:cytology*; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009367:Neoplasm Staging; D009414:Nerve Growth Factors / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009457:Neuroglia / Q000166:cytology*; D000076104:Oligodendrocyte Transcription Factor 2; D010641:Phenotype; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis; D055815:Young Adult
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D051792:Basic Helix-Loop-Helix Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C440408:MIB-1 antibody; C405708:OLIG2 protein, human; C579160:S100B protein, human