title: Involvement of extracellular factors in maintaining self-renewal of neural stem cell by nestin.
abstract: Nestin knockout leads to embryonic lethality and self-renewal deficiency in neural stem cells (NSCs). However, how nestin maintains self-renewal remains uncertain. Here, we used the dosage effect of nestin in heterozygous mice (Nes+/-) to study self-renewal of NSCs. With existing extracellular signaling in vivo or in vitro, nestin levels do not affect proliferation ability or apoptosis when compared between Nes+/- and Nes+/+ NSCs. However, self-renewal ability of Nes+/- NSCs is impaired when plated at a low cell density and completely lost at a clonal density. This deficiency in self-renewal at a clonal density is rescued using a medium conditioned by Nes+/+ NSCs. In addition, the Akt signaling pathway is altered at low density and reversed by conditioned medium. Our data show that secreted factors contribute toward maintaining self-renewal of NSCs by nestin, potentially through Akt signaling.
authors.affiliation: aCenter for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangdong, China bThe Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong, China cDepartment of Neuroscience, Ohio State University Medical Center, Columbus, Ohio, USA.
authors.forename: Chun Guang
authors.initials: CG
authors.lastname: Di
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
authors.forename: Lei
authors.initials: L
authors.lastname: Jia
authors.forename: Jun Feng
authors.initials: JF
authors.lastname: Liu
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Lahn
authors.forename: Bao Feng
authors.initials: BF
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics*; D058953:Neural Stem Cells / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C577485:Nes protein, mouse; D064231:Nestin; D051057:Proto-Oncogene Proteins c-akt