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SRP126053
Mus musculus
1712 Downloadable Samples
Illumina HiSeq 2500
Description
Single-cell RNA sequencing has generated the first catalogs of transcriptionally defined neuronal subtypes of the brain. However, the cellular processes that contribute to neuronal subtype specification and transcriptional heterogeneity remain unclear. By comparing the gene expression profiles of a subset of single layer 6 corticothalamic neurons in somatosensory cortex, we show that transcriptional subtypes primarily reflect axonal projection pattern, laminar position within the cortex, and neuronal activity state. Pseudotemporal ordering of 1023 cellular responses to sensory manipulation demonstrates that changes in expression of activity-induced genes both reinforced cell-type identity and contributed to increased transcriptional heterogeneity within each cell type. This is due to cell-type biased choices of transcriptional states following manipulation of neuronal activity. These results reveal that axonal projection pattern, laminar position, and activity state define significant axes of variation that contribute both to the transcriptional identity of individual neurons and to the transcriptional heterogeneity within each neuronal subtype. Overall design: 1023 single cell RNA-Seq and 6 bulk RNA-seq
Publication Title
Variation in Activity State, Axonal Projection, and Position Define the Transcriptional Identity of Individual Neocortical Projection Neurons.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We compared the transcriptome in E16.5 embryonic mouse cortex isolated by microdissection, in control (+/+) mice and in mice with mutation in frizzled3 (Fzd3) and Celsr3. Overall design: Triplicate RNA samples prepared for each genotype
Publication Title
Feedback regulation of apical progenitor fate by immature neurons through Wnt7-Celsr3-Fzd3 signalling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 758 Downloadable Samples
- Illumina HiSeq 2500
Description
Genetic variation modulating risk of sporadic Parkinson's disease (PD) has been primarily explored through genome wide association studies (GWAS). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal timepoints. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a novel postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including known PD genes and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1 null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Overall design: 473 single cell RNA-Seq samples from sorted mouse Th-eGFP+ dopaminergic neurons collected at two timepoints from three distinct brain regions.
Publication Title
Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We report a transcriptome comparison of HEK293 cells modified at the DPYSL2 gene promoter dinucleotide repeat (chr8:26,435,510-26,435,534) by CRISPR/Cas9 to change from the common 11 repeats to the more rare 13 repeats Overall design: 11/11 repeat HEK 293 cells were modified by CRISPR/Cas 9. Cell were flow sorted by the co-transfected GFP and single cells were expanded. From those we selected 4 modified and 8 unmodified clones for RNA seq. RNA was extracted at 80% confluency
Publication Title
The DPYSL2 gene connects mTOR and schizophrenia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Downregulation of expression and activity levels of the astroglial glutamate transporter EAAT2 is thought to be implicated in motor neuron excitotoxicity in amyotrophic lateral sclerosis (ALS). We previously reported that EAAT2 is cleaved by caspase-3 at the cytosolic C-terminus domain, impairing the transport activity and generating a proteolytic fragment found to be SUMO1 conjugated (CTE-SUMO1). We show here that this fragment accumulates in the nucleus of spinal cord astrocytes in vivo throughout the disease stages of the SOD1-G93A mouse model of ALS. In vitro expression in spinal cord astrocytes of the C-terminus peptide of EAAT2 (CTE), which was artificially fused to SUMO1 (CTE-SUMO1fus) to mimic the endogenous SUMOylation reaction, recapitulates the nuclear accumulation of the fragment seen in vivo and causes caspase-3 activation and axonal growth impairment in motor neuron-derived NSC-34 cells and primary motor neurons co-cultured with CTE-SUMO1fus-expressing spinal cord astrocytes. This indicates that CTE-SUMO1fus could trigger non-cell autonomous mechanisms of neurodegeneration. Prolonged nuclear accumulation of CTE-SUMO1fus in astrocytes leads to their degeneration, although the time frame of the cell-autonomous toxicity is longer than the one for the indirect toxic effect on motor neurons. As more evidence on the implication of SUMO substrates in neurodegenerative diseases emerges, our observations strongly suggest that the nuclear accumulation in spinal cord astrocytes of a SUMOylated proteolytic fragment of the astroglial glutamate transporter EAAT2 could take part to the pathogenesis of ALS and suggest a novel, unconventional role for EAAT2 in motor neuron degeneration in ALS.
Publication Title
Motor neuron impairment mediated by a sumoylated fragment of the glial glutamate transporter EAAT2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
After inactivation of Hoxa5 at postnatal days (P)1-P4, we established RNA-seq profiling with RNA extracted from P21 brainstem of tamoxifen-treated Hoxa5flox/flox;CMV-CreERT2+/- (Hoxa5 cKO) pups and tamoxifen-treated Hoxa5flox/flox;CMV-CreERT2-/-(Hoxa5 control) pups Overall design: To explore HOXA5 downstream target genes in the postnatal brainstem, we carried out transcriptomic analyses by RNA-Seq using a model of postnatal Hoxa5 loss-of-function. We induced Hoxa5 inactivation after birth (P1 to P4) using the tamoxifen-inducible CMV-CreERT2 mice and conditional Hoxa5 floxed allele mice (Hoxa5flox). RNA was extracted from the brainstem of P21 tamoxifen-treated Hoxa5flox/flox;CMV-CreERT2+/- pups and from tamoxifen-treated Hoxa5flox/flox;CMV-CreERT2-/- littermates (see extract protocol).
Publication Title
Conditional Loss of <i>Hoxa5</i> Function Early after Birth Impacts on Expression of Genes with Synaptic Function.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The RET/PTC3 (RP3) fusion gene is the most frequent mutation found in radiation-induced papillary thyroid cancers (PTC). Several studies suggest that the RET/PTC rearrangement is an initiating event in tumorigenesis. E7 is an oncoprotein derived from the Human Papilllomavirus 16 (HPV16) responsible for most cervical carcinoma in women. We studied here the sequence of events leading to thyroid cancer in Tg-RP3 and Tg-E7 mice expressing the transgene exclusively in the thyroid under the control of thyroglobulin (Tg) promoter. Both transgenic mice develop thyroid hyperplasia followed by solid differentiated carcinoma in older animals. To understand the different steps leading to carcinoma, we analyzed thyroid gene expression in both strains at different ages (2, 6, 10 months) by microarray technology. Important biological processes were differentially regulated in the two tumor types. In E7 thyroids cell cycle was the most upregulated process; observation consistent with the huge size of these tumors. In RP3 thyroids immunity was the most significantly regulated process, as previously observed in microarray data on human PTC. Interestingly, other human PTC characteristics were also observed in RP3 but not in E7 mouse tumors: similar regulation of several human PTC markers, upregulation of many EGF-like growth factors and finally significant regulation of angiogenesis and extracellular matrix remodeling-related genes. In summary we showed that RP3 contrary to E7 mouse tumors share several important genotypic characteristics with human PTC, observation reinforcing the validity of this model to study human thyroid tumorigenesis.
Publication Title
Gene expression in RET/PTC3 and E7 transgenic mouse thyroids: RET/PTC3 but not E7 tumors are partial and transient models of human papillary thyroid cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2000
Description
Mutations in MECP2 cause Rett syndrome (RTT), a X-linked neurological disorder characterized by the regressive loss of neurodevelopmental milestones and acquired intellectual disability and motor impairments. However, the cellular heterogeneity of the mammalian brain impedes our understanding of how MECP2 mutations disrupt neuronal function and contribute to RTT. In response, we developed cell type-specific biotin tagging in mice bearing RTT-associated mutations and profiled nuclear transcriptomes in WT and mutant neurons. Although individual gene expression changes are largely specific to each mutation and cell type, higher-level transcriptional features remain conserved and correlate with RTT phenotypic severity. Furthermore, subcellular RNA populations support post-transcriptional compensation as a basis for the upregulation of long genes previously reported in RTT mutant neurons. Finally, we overcame the genetic mosacism associated with female RTT mouse models and identified functionally distinct gene expression changes in neighboring WT and mutant neurons, which altogether provide key contextual insights into RTT. Overall design: Nuclear total RNA-seq of two types of neurons of male and female RTT mice and GRO-seq of the cortex
Publication Title
Biotin tagging of MeCP2 in mice reveals contextual insights into the Rett syndrome transcriptome.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Corticospinal motor neurons (CSMN) are one specialized class of cortical excitatory neurons, which connect layer Vb of the cortex to the spinal cord. a master transcription factor Forebrain expressed zinc finger 2 (Fezf2) has been identified that is necessary for the fate specification of CSMN. Fezf2 alone can cell-autonomously instruct the acquisition of CSMN-specific features when expressed in diverse, permissive cellular contexts, in vivo.
Publication Title
Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Long noncoding RNAs regulate adipogenesis.
Sample Metadata Fields
Specimen part, Disease
View Samples