Open AccessSurfaceome Profiling Reveals Regulators of Neural Stem Cell Function
Author(s) -
DeVeale Brian,
Bausch-Fluck Damaris,
Seaberg Raewyn,
Runciman Susan,
Akbarian Vahe,
Karpowicz Phillip,
Yoon Charles,
Song Hannah,
Leeder Rachel,
Zandstra Peter W.,
Wollscheid Bernd,
Kooy Derek
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1550
Subject(s) - biology , neural stem cell , embryonic stem cell , microbiology and biotechnology , stem cell , induced pluripotent stem cell , genetics , gene
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. S tem C ells 2014;32:258–268