title: CSPG is a secreted factor that stimulates neural stem cell survival possibly by enhanced EGFR signaling.
abstract: Understanding how autocrine/paracrine factors regulate neural stem cell (NSC) survival and growth is fundamental to the utilization of these cells for therapeutic applications and as cellular models for the brain. In vitro, NSCs can be propagated along with neural progenitors (NPs) as neurospheres (nsphs). The nsph conditioned medium (nsph-CM) contains cell-secreted factors that can regulate NSC behavior. However, the identity and exact function of these factors within the nsph-CM has remained elusive. We analyzed the nsph-CM by mass spectrometry and identified DSD-1-proteoglycan, a chondroitin sulfate proteoglycan (CSPG), apolipoprotein E (ApoE) and cystatin C as components of the nsph-CM. Using clonal assays we show that CSPG and ApoE are responsible for the ability of the nsph-CM to stimulate nsph formation whereas cystatin C is not involved. Clonal nsphs generated in the presence of CSPG show more than four-fold increase in NSCs. Thus CSPG specifically enhances the survival of NSCs. CSPG also stimulates the survival of embryonic stem cell (ESC)-derived NSCs, and thus may be involved in the developmental transition of ESCs to NSCs. In addition to its role in NSC survival, CSPG maintains the three dimensional structure of nsphs. Lastly, CSPG's effects on NSC survival may be mediated by enhanced signaling via EGFR, JAK/STAT3 and PI3K/Akt pathways.
authors.affiliation: Neural Stem Cell Laboratory, Institute of Medical Biology, Singapore, Singapore.
authors.forename: Muly
authors.initials: M
authors.lastname: Tham
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ramasamy
authors.forename: Hui Theng
authors.initials: HT
authors.lastname: Gan
authors.forename: Ashray
authors.initials: A
authors.lastname: Ramachandran
authors.forename: Anuradha
authors.initials: A
authors.lastname: Poonepalli
authors.forename: Yuan Hong
authors.initials: YH
authors.lastname: Yu
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D055316:Cystatin C / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology; D066246:ErbB Receptors / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology; D009474:Neurons / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*
chemical_list: D001057:Apolipoproteins E; D011508:Chondroitin Sulfate Proteoglycans; D017077:Culture Media, Conditioned; D055316:Cystatin C; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors