title: Identification of proteomic changes during differentiation of adult mouse subventricular zone progenitor cells.
abstract: The use of neural precursor cells (NPCs) represents a promising repair strategy for many neurological disorders. However, the molecular events and biological features that control NPC proliferation and their differentiation into neurons, astrocytes, and oligodendrocytes are unclear. In the present study, we used a comparative proteomics approach to identify proteins that were differentially regulated in NPCs after short-term differentiation. We also used a subcellular fractionation technique for enrichment of nuclei and other dense organelles to identify proteins that were not readily detected in whole cell extracts. In total, 115 distinct proteins underwent expression changes during NPC differentiation. Forty one of these were only identified following subcellular fractionation. These included transcription factors, RNA-processing factors, cell cycle proteins, and proteins that translocate between the nucleus and cytoplasm. Biological network analysis showed that the differentiation of NPCs was associated with significant changes in cell cycle and protein synthesis machinery. Further characterization of these proteins could provide greater insight into the mechanisms involved in regulation of neurogenesis in the adult central nervous system (CNS) and potentially identify points of therapeutic intervention.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, United Kingdom. kamran.salim@immunobiology.co.uk
authors.forename: Kamran
authors.initials: K
authors.lastname: Salim
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.forename: Heather A
authors.initials: HA
authors.lastname: Skynner
authors.forename: James G
authors.initials: JG
authors.lastname: Bilsland
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Bonnert
authors.forename: George
authors.initials: G
authors.lastname: McAllister
authors.forename: Ignacio
authors.initials: I
authors.lastname: Munoz-Sanjuan
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002453:Cell Cycle; D002454:Cell Differentiation; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology* / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010449:Peptide Mapping; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins