title: Transcriptional profiling of adult neural stem-like cells from the human brain.
abstract: There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.
authors.affiliation: Vilhelm Magnus Lab, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
authors.forename: Cecilie Jonsgar
authors.initials: CJ
authors.lastname: Sandberg
authors.affiliation: Vilhelm Magnus Lab, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
authors.forename: Einar O
authors.initials: EO
authors.lastname: Vik-Mo
authors.affiliation: Vilhelm Magnus Lab, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
authors.forename: Jinan
authors.initials: J
authors.lastname: Behnan
authors.affiliation: Vilhelm Magnus Lab, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Helseth
authors.affiliation: Vilhelm Magnus Lab, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, Oslo, Norway; Cancer Stem Cell Innovation Center (CAST), Oslo University Hospital and University of Oslo, Oslo, Norway; Norwegian Stem Cell Center, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Iver A
authors.initials: IA
authors.lastname: Langmoen
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism*; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D046228:Microarray Analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; C489356:KCNS3 protein, human; D008565:Membrane Proteins; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D017475:Receptors, Nerve Growth Factor; C581991:Slitrk6 protein, human