title: Continuous live imaging of adult neural stem cell division and lineage progression in vitro.
abstract: Little is known about the intrinsic specification of adult neural stem cells (NSCs) and to what extent they depend on their local niche. To observe adult NSC division and lineage progression independent of their niche, we isolated cells from the adult mouse subependymal zone (SEZ) and cultured them at low density without growth factors. We demonstrate here that SEZ cells in this culture system are primarily neurogenic and that adult NSCs progress through stereotypic lineage trees consisting of asymmetric stem cell divisions, symmetric transit-amplifying divisions and final symmetric neurogenic divisions. Stem cells, identified by their astro/radial glial identity and their slow-dividing nature, were observed to generate asymmetrically and fast-dividing cells that maintained an astro/radial glia identity. These, in turn, gave rise to symmetrically and fast-dividing cells that lost glial hallmarks, but had not yet acquired neuronal features. The number of amplifying divisions was limited to a maximum of five in this system. Moreover, we found that cell growth correlated with the number of subsequent divisions of SEZ cells, with slow-dividing astro/radial glia exhibiting the most substantial growth prior to division. The fact that in the absence both of exogenously supplied growth factors and of signals provided by the local niche neurogenic lineage progression takes place in such stereotypic fashion, suggests that lineage progression is, to a significant degree, cell intrinsic or pre-programmed at the beginning of the lineage.
authors.affiliation: Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, 59072-970 Natal, Brazil. mrcosta@neuro.ufrn.br
authors.forename: Marcos R
authors.initials: MR
authors.lastname: Costa
authors.forename: Felipe
authors.initials: F
authors.lastname: Ortega
authors.forename: Monika S
authors.initials: MS
authors.lastname: Brill
authors.forename: Ruth
authors.initials: R
authors.lastname: Beckervordersandforth
authors.forename: Ciro
authors.initials: C
authors.lastname: Petrone
authors.forename: Timm
authors.initials: T
authors.lastname: Schroeder
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
authors.forename: Benedikt
authors.initials: B
authors.lastname: Berninger
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods*; D002478:Cells, Cultured; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D009420:Nervous System / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D036341:Intercellular Signaling Peptides and Proteins