title: 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.
authors: CRTD-Center for Regenerative Therapies Dresden, Technische Universität Dresden, 01307 Dresden, Germany. tara.walker@crt-dresden.de
authors: Tara L
authors: TL
authors: Walker
authors: Ann
authors: A
authors: Wierick
authors: Alex M
authors: AM
authors: Sykes
authors: Ben
authors: B
authors: Waldau
authors: Denis
authors: D
authors: Corbeil
authors: Peter
authors: P
authors: Carmeliet
authors: Gerd
authors: G
authors: Kempermann
mesh_terms: D000071916:AC133 Antigen; D053687:Adult Stem Cells / Q000187:drug effects*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002448:Cell Adhesion; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D018076:DNA, Complementary / Q000096:biosynthesis; D018891:Dentate Gyrus / Q000378:metabolism; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000187:drug effects*; D010455:Peptides / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms; D012313:RNA / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000963:Antimetabolites; D018076:DNA, Complementary; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D010455:Peptides; C000606024:Prom1 protein, mouse; C473220:Prom2 protein, mouse; D020033:Protein Isoforms; D012313:RNA; D001973:Bromodeoxyuridine