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Series GSE65970 Query DataSets for GSE65970
Status Public on Jan 12, 2018
Title Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The adult mouse subependymal zone (SEZ) provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem cell number within a shared niche fluctuates over time. Fate-mapping proliferating cells using a novel Ki67iresCreER allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a novel niche-based mechanism for the regulation of NSC fate and number.
Overall design We analysed the adult mouse subependymal zone (SEZ), the largest neruogenic niche in the brain, at a single cell level. For this, we used SORT-seq, a combination of FACS and single cell RNA-sequencing that resulted in high quality transcriptome data from ~1500 single cells (out of ~2500 cells sequenced). To identify different cell types, we used knock-in mouse models, surface labeling using antibdoies as well as lineage tracing. Troy-GFPiresCreER +/ki mice were used to identify NSCs. Ki67-tagRFP ki/ki mice were used to identify dividing cells. Ki67-iresCreER +/ki Rosa-tdTomato +/ki mice were administered a single injection of 5mg of Tamoxifen to label dividing cells (day2 - d2) and follow their progeny (day60 - d60) in the SEZ as well as the olfactory bulb (for d60 only). We also included published markers; combinations of anti-GLAST antibody (to identify NSCs) and EGF binding ability using alexa647-conjugated EGF (to identify dividing cells), combinations of anti-Prom1 (Cell contacting the ventricles) and anti-CD24 antibodies (high in neuroblasts), as well as anti-O4 antibody (oligodendrocytes) to create an atlas of NSCs.
Contributor(s) Basak O, Krieger TG, Muraro MJ, Wiebrands K, Stange DE, Aldeguer JF, Rivron NC, van de Wetering M, van Es JH, van Oudenaarden A, Simons BD, Clevers H
Citation(s) 29311336
Submission date Feb 17, 2015
Last update date May 31, 2019
Contact name Onur BASAK
Organization name Hubrecht Institute
Lab Clevers
Street address Uppsalalaan 8
City Utrecht
ZIP/Postal code 3584CT
Country Netherlands
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (28)
BioProject PRJNA275609
SRA SRP055081

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Supplementary file Size Download File type/resource
GSE65970_RAW.tar 9.1 Mb (http)(custom) TAR (of CSV)
GSE65970_cel-seq_barcodes.csv.gz 424 b (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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