Flatworms of the species are immortal-adult animals contain a large pool of pluripotent stem cells that continuously differentiate into all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterized gene expression changes during differentiation and discovered cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution.

Highlights d Single-cell transcriptomics characterizes the SVZ adult neural stem cell niche d Free online tool to assess gene expression across 9,804 single cells d Different transcriptional dynamics along the neurogenic lineage d Cell-type-specific dysfunctions underlying impaired adult neurogenesis

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article.

Neural stem cells (NSCs) contribute to plasticity and repair of the adult brain. Niches harboring NSCs are crucial for regulating stem cell self-renewal and differentiation. We used single-cell RNA profiling to generate an unbiased molecular atlas of all cell types in the largest neurogenic niche of the adult mouse brain, the subventricular zone (SVZ). We characterized > 20 neural and non-neural cell types and gained insights into the dynamics of neurogenesis by predicting future cell states based on computational analysis of RNA kinetics. Furthermore, we apply our single-cell approach to mice lacking LRP2, an endocytic receptor required for SVZ maintenance. The number of NSCs and proliferating progenitors was significantly reduced. Moreover, Wnt and BMP4 signaling was perturbed. We provide a valuable resource for adult neurogenesis, insights into SVZ neurogenesis regulation by LRP2, and a proof-of-principle demonstrating the power of single-cell RNA-seq in pinpointing neural cell type-specific functions in loss-of-function models. KEYWORDSadult neurogenesis, neurogenic niche, single-cell RNA sequencing, adult neural stem cells, subventricular zone, LDL-receptor related protein, RNA velocity HIGHLIGHTS  unbiased single-cell transcriptomics characterizes adult NSCs and their niche  cell type-specific signatures and marker genes for 22 SVZ cell types  Free online tool to assess gene expression across 9,804 single cells  cell type-specific dysfunctions underlying impaired adult neurogenesis

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