Molecular characterization of adult mouse subventricular zone progenitor cells during the onset of differentiation.
Adult mouse subventricular zone (SVZ) neural progenitor cells (NPCs) retain the capacity to generate multiple lineages in vitro and in vivo. Thus far, the mechanisms involved in the regulation of these cells have not been well elucidated. We have carried out RNA profiling of adult SVZ cell cultures undergoing differentiation, to identify pathways that regulate progenitor cell proliferation and to define a set of transcripts that can be used as molecular tools in the drug discovery process. We carried out a stepwise stratification of the results to identify transcripts specifically enriched in NPCs and validated some of these using comparative literature analysis, quantitative polymerase chain reaction and immunological techniques. The results show a set of transcription factors, secreted molecules and plasma membrane markers that are differentially regulated during differentiation. Pathway analysis highlights alterations in insulin growth factor, Wnt and transforming growth factor beta signalling cascades. Further characterization of these components could provide greater insight into the mechanisms involved in the regulation of neurogenesis in the adult brain.
Bonnert
Timothy P
TP
Molecular and Cellular Neuroscience Department, Merck Sharp & Dohme, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK.
Bilsland
James G
JG
Guest
Paul C
PC
Heavens
Robert
R
McLaren
Donna
D
Dale
Charlotte
C
Thakur
Matthew
M
McAllister
George
G
Munoz-Sanjuan
Ignacio
I
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D020547:Lateral Ventricles / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D040901:Proteomics; D015398:Signal Transduction / Q000502:physiology*; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D006133:Growth Substances; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D013002:Somatomedins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins