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Abstract
Neural stem cells (NSCs) reside in a unique microenvironment called the neurogenic niche and generate functional new neurons. The neurogenic niche contains several distinct types of cells and interacts with the NSCs in the subventricular zone (SVZ) of the lateral ventricle. While several molecules produced by the niche cells have been identified to regulate adult neurogenesis, a systematic profiling of autocrine/paracrine signaling molecules in the neurogenic regions involved in maintenance, self-renewal, proliferation, and differentiation of NSCs has not been done. We took advantage of the genetic inducible fate mapping system (GIFM) and transgenic mice to isolate the SVZ niche cells including NSCs, transit-amplifying progenitors (TAPs), astrocytes, ependymal cells, and vascular endothelial cells. From the isolated cells and microdissected choroid plexus, we obtained the secretory molecule expression profiling (SMEP) of each cell type using the Signal Sequence Trap method. We identified a total of 151 genes encoding secretory or membrane proteins. In addition, we obtained the potential SMEP of NSCs using cDNA microarray technology. Through the combination of multiple screening approaches, we identified a number of candidate genes with a potential relevance for regulating the NSC behaviors, which provide new insight into the nature of neurogenic niche signals.
Highlights
In the postnatal mammalian brain, neural stem cells (NSCs) are retained in a unique compartment after embryonic development and generate new cells throughout the life of an animal
In order to gain a better understanding of how Neural stem cells (NSCs) communicate with surrounding niche cells, we aim to provide a systematic profiling of signaling molecules in the subventricular zone (SVZ) neurogenic niche in a cell-type specific manner in this study
We isolated the NSCs and transit-amplifying progenitors (TAPs) based on their responsiveness to Sonic hedgehog (Shh) signaling and Gli1 expression in the SVZ [23]
Summary
In the postnatal mammalian brain, neural stem cells (NSCs) are retained in a unique compartment after embryonic development and generate new cells throughout the life of an animal. While the cells in the non-neurogenic regions do not produce new cells in vivo, they can become neurogenic under proper culture conditions in vitro, indicating the importance of the permissive environment in which NSCs reside. Such a specialized microenvironment is called the NSC niche and provides the appropriate cues that regulate NSC behaviors, such as maintenance, self-renewal, proliferation, and generation of progenies [4,5]. The nature of niche signals is not fully elucidated
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