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Prominin-1 (CD133) is a commonly used cancer stem cell marker in central nervous system (CNS) tumors including glioblastoma (GBM). Expression of Prom1 in cancer is thought to parallel expression and function in normal stem cells. Using RNA in situ hybridization and antibody tools capable of detecting multiple isoforms of Prom1, we find evidence for two distinct  Prom1  cell populations in mouse brain.  Prom1  RNA is first expressed in stem/progenitor cells of the ventricular zone in embryonic brain. Conversely, in adult mouse brain  Prom1  RNA is low in SVZ/SGZ stem cell zones but high in a rare but widely distributed cell population ( Prom1 hi  ). Lineage marker analysis reveals  Prom1 hi   cells are Olig2+Sox2+ glia but  Olig1/2  knockout mice lacking oligodendroglia retain  Prom1 hi   cells. Bromodeoxyuridine labeling identifies  Prom1 hi   as slow-dividing distributed progenitors distinct from NG2+Olig2+ oligodendrocyte progenitors. In adult human brain, PROM1 cells are rarely positive for OLIG2, but express astroglial markers GFAP and SOX2. Variability of PROM1 expression levels in human GBM and patient-derived xenografts (PDX) – from no expression to strong, uniform expression – highlights that PROM1 may not always be associated with or restricted to cancer stem cells. TCGA and PDX data show that high expression of  PROM1  correlates with poor overall survival. Within proneural subclass tumors, high  PROM1  expression correlates inversely with  IDH1  (R132H) mutation. These findings support PROM1 as a tumor cell-intrinsic marker related to GBM survival, independent of its stem cell properties, and highlight potentially divergent roles for this protein in normal mouse and human glia.

Prominin-1 (CD133) Defines Both Stem and Non-Stem Cell Populations in CNS Development and Gliomas