Project description:The striatum contributes to many cognitive processes and disorders, but its cell types are incompletely characterized. We show that microfluidic and FACS-based single-cell RNA sequencing of mouse striatum provides a well-resolved classification of striatal cell type diversity. Transcriptome analysis revealed 10 differentiated distinct cell types, including neurons, astrocytes, oligodendrocytes, ependymal, immune, and vascular cells, and enabled the discovery of numerous novel marker genes. Furthermore, we identified two discrete subtypes of medium spiny neurons (MSN) which have specific markers and which overexpress genes linked to cognitive disorders and addiction. We also describe continuous cellular identities, which increase heterogeneity within discrete cell types. Finally, we identified cell type specific transcription and splicing factors that shape cellular identities by regulating splicing and expression patterns. Our findings suggest that functional diversity within a complex tissue arises from a small number of discrete cell types, which can exist in a continuous spectrum of functional states. We measured the transcriptome of 1208 single striatal cells using two complementary approaches; microfluidic single-cell RNAseq (Mic-scRNAseq) and single cell isolation by FACS (FACS-scRNAseq) (Table S1). We sampled cells either randomly or enriched specifically for MSNs or astrocytes using FACS from D1- tdTomato (tdTom)/D2-GFP or Aldhl1-GFP mice, respectively
Project description:In order to investigate age-dependent mRNA expression in mouse striatal interneurons, we performed single cell RNA-seq on FACS-isolated fluorescently labeled cells from the dorsal striatum of two mouse lines, 5ht3aEGFP or Lhx6cre::R26R-tdTomat, from either P21-26 or P55-76 animals. We included the ventricular side of the striatum that contains adult born neuroblasts destined for the olfactory bulb.
Project description:Gene expression profiling of striatum in R6/2 Huntington’s disease (HD) model mouse. Striatum gene set contained gene expression alterations in other neuronal populations, such as oligodendrocyte, astrocyte, microglia and interneuron.
Project description:Nicotine withdrawal can diversely affect brain gene expression patterns. In the brain, the dorsal striatum is a hub of nicotine dependence. Previous studies have shown that nicotine dependence leads to functional alterations in the dorsal striatum. miRNAs are small non-coding RNAs that regulates cellular functions and dysfunctions. Here, we performed small RNA sequencing from the dorsal striatum of mice at 7 days after nicotine withdrawal. Our results show that nicotine withdrawal does not notably impact miRNA expression profile in the dorsal striatum, but a few miRNAs were significantly altered in response to nicotine withdrawal. These results suggest that nicotine withdrawal has a small but significant impact on the miRNA expression profile in the mouse dorsal striatum.