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Prominin-1 allows prospective isolation of neural stem cells from the adult murine hippocampus.

Abstract
Prominin-1 (CD133) is commonly used to isolate stem and progenitor cells from the developing and adult nervous system and to identify cancer stem cells in brain tumors. However, despite extensive characterization of Prominin-1(+) precursor cells from the adult subventricular zone, no information about the expression of Prominin-1 by precursor cells in the subgranular zone (SGZ) of the adult hippocampus has been available. We show here that Prominin-1 is expressed by a significant number of cells in the SGZ of adult mice in vivo and ex vivo, including postmitotic astrocytes. A small subset of Prominin-1(+) cells coexpressed the nonspecific precursor cell marker Nestin as well as GFAP and Sox2. Upon fluorescence-activated cell sorting, only Prominin-1/Nestin double-positive cells fulfilled the defining stem cell criteria of proliferation, self-renewal, and multipotentiality as assessed by a neurosphere assay. In addition, isolated primary Prominin-1(+) cells preferentially migrated to the neurogenic niche in the SGZ upon transplantation in vivo. Finally, despite its expression by various stem and progenitor cells, Prominin-1 turned out to be dispensable for precursor cell proliferation in vitro and in vivo. Nevertheless, a net decrease in hippocampal neurogenesis, by ∼30% was found in Prominin-1 knock-out mice, suggesting other roles in controlling adult hippocampal neurogenesis. Remarkably, an upregulation of Prominin-2 was detected in Prominin-1-deficient mice highlighting a potential compensatory mechanism, which might explain the lack of severe symptoms in individuals carrying mutations in the Prom1 gene.
AuthorsTara L Walker, Ann Wierick, Alex M Sykes, Ben Waldau, Denis Corbeil, Peter Carmeliet, Gerd Kempermann
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 33 Issue 7 Pg. 3010-24 (Feb 13 2013) ISSN: 1529-2401 [Electronic] United States
PMID23407958 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AC133 Antigen
  • Antigens, CD
  • Antimetabolites
  • DNA, Complementary
  • Glycoproteins
  • Intermediate Filament Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Peptides
  • Prom1 protein, mouse
  • Prom2 protein, mouse
  • Protein Isoforms
  • RNA
  • Bromodeoxyuridine
Topics
  • AC133 Antigen
  • Adult Stem Cells (drug effects)
  • Animals
  • Antigens, CD (genetics, metabolism)
  • Antimetabolites
  • Bromodeoxyuridine
  • Cell Adhesion
  • Cell Cycle (drug effects)
  • Cell Differentiation
  • Cell Proliferation
  • Cell Separation (methods)
  • DNA, Complementary (biosynthesis)
  • Dentate Gyrus (metabolism)
  • Flow Cytometry
  • Glycoproteins (genetics, metabolism)
  • Hippocampus (cytology, drug effects)
  • Immunohistochemistry
  • Intermediate Filament Proteins (genetics, metabolism)
  • Membrane Glycoproteins (biosynthesis, genetics)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins (genetics, metabolism)
  • Nestin
  • Neural Stem Cells (drug effects)
  • Peptides (genetics, metabolism)
  • Protein Isoforms
  • RNA (isolation & purification)
  • Real-Time Polymerase Chain Reaction

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