title: Surfaceome profiling reveals regulators of neural stem cell function.
abstract: The composition of cell-surface proteins changes during lineage specification, altering cellular responses to their milieu. The changes that characterize maturation of early neural stem cells (NSCs) remain poorly understood. Here we use mass spectrometry-based cell surface capture technology to profile the cell surface of early NSCs and demonstrate functional requirements for several enriched molecules. Primitive NSCs arise from embryonic stem cells upon removal of Transforming growth factor-β signaling, while definitive NSCs arise from primitive NSCs upon Lif removal and FGF addition. In vivo aggregation assays revealed that N-cadherin upregulation is sufficient for the initial exclusion of definitive NSCs from pluripotent ectoderm, while c-kit signaling limits progeny of primitive NSCs. Furthermore, we implicate EphA4 in primitive NSC survival signaling and Erbb2 as being required for NSC proliferation. This work elucidates several key mediators of NSC function whose relevance is confirmed on forebrain-derived populations and identifies a host of other candidates that may regulate NSCs.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: DeVeale
authors.forename: Damaris
authors.initials: D
authors.lastname: Bausch-Fluck
authors.forename: Raewyn
authors.initials: R
authors.lastname: Seaberg
authors.forename: Susan
authors.initials: S
authors.lastname: Runciman
authors.forename: Vahe
authors.initials: V
authors.lastname: Akbarian
authors.forename: Phillip
authors.initials: P
authors.lastname: Karpowicz
authors.forename: Charles
authors.initials: C
authors.lastname: Yoon
authors.forename: Hannah
authors.initials: H
authors.lastname: Song
authors.forename: Rachel
authors.initials: R
authors.lastname: Leeder
authors.forename: Peter W
authors.initials: PW
authors.lastname: Zandstra
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollscheid
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D034741:RNA, Small Interfering
keywords: Developmental gene expression regulation; Embryonic development; Membrane glycoproteins; Neural stem cells