Continuous and discrete neuron types of the adult murine striatum
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PROVIDER: PRJNA589979 | ENA |
REPOSITORIES: ENA
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Project description:The mammalian striatum is involved in many complex behaviors and yet is largely composed of a single neuron class: the spiny projection neuron (SPN). It is unclear to what extent the functional specialization of the striatum is due to the molecular specialization of SPN subtypes. We sought to define the molecular and anatomical diversity of adult SPNs using single-cell RNA-seq and quantitative RNA in situ hybridization (ISH). We computationally distinguished discrete versus continuous heterogeneity in scRNA-seq data and found that SPNs in the striatum can be classified into four major discrete types with no implied spatial relationship between them. Within these discrete types, we find continuous heterogeneity encoding spatial gradients of gene expression and defining anatomical location in a combinatorial mechanism. Our results suggest that neuronal circuitry has a substructure at far higher resolution than is typically interrogated which is defined by the precise identity and location of a neuron.
2019-11-17 | GSE139412 | GEO
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.
2016-07-15 | GSE82187 | GEO
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
2016-07-15 | E-GEOD-82187 | biostudies-arrayexpress
Project description:Discrete and continuous heterogeneity in the basolateral amygdala
| PRJNA625988 | ENA
Project description:The brain is composed of millions of diverse neurons that differ systematically in the genes that they express. Analyses of single cell gene expression data reveal clusters which correspond to different cell types that differ in their connectivity and function. Can the connections formed by genetically identical neurons systematically alter their gene expression? Here we address this question by combining retrograde labeling, single cell gene expression, and rabies-based analyses of connectivity to assess cortical-cortical projection neurons in the mouse primary visual cortex. We find that pyramidal neurons projecting to different cortical targets and with known functional differences differ systematically in their gene expression and connectivity despite forming only a single genetic cluster with continuous variability. These observations demonstrate that single cell gene expression analysis in isolation is insufficient to identify neuron types.
2020-07-25 | GSE133230 | GEO
Project description:Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases. RNA-seq of mRNA levels in 197 individual DRG neurons We performed RNA-seq on total 203 individual DRG neurons. Six of them were not qualified and thus, were excluded for further analysis. To evaluate the quality of RNA-seq, we randomly devided No.72 neurons into two parts and performed RNA-seq seperately. Thus, we had 204 individual samples from 203 individual DRG and 198 individual qualified samples from 197 individual DRG. To evaluate the homogeneity of RNA-seq data from different mice at the same age just as used, we performed RNA-seq on 5 single DRG from different mice. Here, these data from DRG were also considered as experimental control. The 'DRG_neurons_RNA_Seq.txt' contains processed data for 204 samples and 'DRG_RNA_Seq.txt' for 5 samples.
2015-12-10 | E-GEOD-63576 | biostudies-arrayexpress
Project description:Extraction of Distinct Cell Types from within a Genetically Continuous Population
| PRJNA550420 | ENA
Project description:Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases.
2015-12-10 | GSE63576 | GEO
Project description:Basolateral excitatory neurons constitute a prominent output neuron class of the amygdala. Here, we examined diversity in this cell type using single-cell RNA-seq.
2020-08-28 | GSE148866 | GEO
Project description:Proprioception is governed by highly diverse and versatile sensory neuron types
| PRJNA657004 | ENA