title: Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells.
abstract: Specialized niches support the lifelong maintenance and function of tissue-specific stem cells. Adult neural stem cells in the ventricular-subventricular zone (V-SVZ) contact the cerebrospinal fluid (CSF), which flows through the lateral ventricles. A largely ignored component of the V-SVZ stem cell niche is the lateral ventricle choroid plexus (LVCP), a primary producer of CSF. Here we show that the LVCP, in addition to performing important homeostatic support functions, secretes factors that promote colony formation and proliferation of purified quiescent and activated V-SVZ stem cells and transit-amplifying cells. The functional effect of the LVCP secretome changes throughout the lifespan, with activated neural stem cells being especially sensitive to age-related changes. Transcriptome analysis identified multiple factors that recruit colony formation and highlights novel facets of LVCP function. Thus, the LVCP is a key niche compartment that translates physiological changes into molecular signals directly affecting neural stem cell behavior.
authors.affiliation: Biozentrum, University of Basel, 4056 Basel, Switzerland; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Violeta
authors.initials: V
authors.lastname: Silva-Vargas
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032, USA.
authors.forename: Angel R
authors.initials: AR
authors.lastname: Maldonado-Soto
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Dogukan
authors.initials: D
authors.lastname: Mizrak
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Codega
authors.affiliation: Biozentrum, University of Basel, 4056 Basel, Switzerland; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA. Electronic address: fiona.doetsch@unibas.ch.
authors.forename: Fiona
authors.initials: F
authors.lastname: Doetsch
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D002831:Choroid Plexus / Q000166:cytology* / Q000378:metabolism; D002999:Clone Cells; D020869:Gene Expression Profiling; D020547:Lateral Ventricles / Q000166:cytology; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D055153:Stem Cell Niche