Until now, limitations in the ability to enrich adult NSCs (aNSCs) have hampered meaningful analysis of these cells at the transcriptome level. Here we show via a split-Cre technology that coincident activity of the hGFAP and prominin1 promoters is a hallmark of aNSCs in vivo. Sorting of cells from the adult mouse subependymal zone (SEZ) based on their expression of GFAP and prominin1 isolates all self-renewing, multipotent stem cells at high purity. Comparison of the transcriptome of these purified aNSCs to parenchymal nonneurogenic astrocytes and other SEZ cells reveals aNSC hallmarks, including neuronal lineage priming and the importance of cilia- and Ca-dependent signaling pathways. Inducible deletion of the ciliary protein IFT88 in aNSCs validates the role of ciliary function in aNSCs. Our work reveals candidate molecular regulators for unique features of aNSCs and facilitates future selective analysis of aNSCs in other functional contexts, such as aging and injury.

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Neural stem cells (NSCs) generate new hippocampal dentate granule neurons throughout adulthood. The genetic programs controlling neuronal differentiation of adult NSCs are only poorly understood. Here we show that, in the adult mouse hippocampus, expression of the SoxC transcription factors Sox4 and Sox11 is initiated around the time of neuronal commitment of adult NSCs and is maintained in immature neurons. Overexpression of Sox4 and Sox11 strongly promotes in vitro neurogenesis from adult NSCs, whereas ablation of Sox4/Sox11 prevents in vitro and in vivo neurogenesis from adult NSCs. Moreover, we demonstrate that SoxC transcription factors target the promoters of genes that are induced on neuronal differentiation of adult NSCs. Finally, we show that reprogramming of astroglia into neurons is dependent on the presence of SoxC factors. These data identify SoxC proteins as essential contributors to the genetic network controlling neuronal differentiation in adult neurogenesis and neuronal reprogramming of somatic cells.

In the mammalian brain, neural stem and progenitor cells in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus generate new neurons throughout adulthood. The generation of new functional neurons is a complex process that is tightly controlled by extrinsic signals and that is characterized by stage-specific gene expression programs and cell biological processes. The transcription factors regulating such stage-specific developmental steps in adult neurogenesis are largely unknown. Here we report that Sox11, a member of the group C Sox transcription factor family, is prominently expressed in the neurogenic areas of the adult brain. Further analysis revealed that Sox11 expression is strictly confined to doublecortin-expressing neuronally committed precursors and immature neurons but that Sox11 is not expressed in non-committed Sox2-expressing precursor cells and mature neurons of the adult neurogenic lineage. Finally, overexpression of Sox11 promotes the generation of doublecortin-positive immature neurons from adult neural stem cells in vitro. These data indicate that Sox11 is involved in the transcriptional regulation of specific gene expression programs in adult neurogenesis at the stage of the immature neuron.