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Series GSE145273 Query DataSets for GSE145273
Status Public on Jul 22, 2020
Title Integrated single-cell analysis reveals coupled molecular gradient and functional subnetworks in the thalamic reticular nucleus
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, is known to regulate thalamocortical interactions critical for sensory processing, attention and cognition. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders. Currently, little is known about the organizational principles underlying its divergent functions. We performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that TRN cellular heterogeneity is characterized by a transcriptomic gradient of two negatively correlated gene expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core/shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections to the functionally distinct first-order and higher order thalamic nuclei to form molecularly defined TRN-thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. Taken together, our study provides a comprehensive atlas for TRN neurons at the single-cell resolution, and links molecularly defined subnetworks to the functional organization of the thalamo-cortical circuits.
Overall design The project involved 8 plates of TRN nuclei with NeuN selection, 9 plates of TRN nuclei without NeuN selection, 4 plates of TRN-adjacent (Thalamus and Globus Pallidus) nuclei, 7 plates hippocampus Pvalb+ nuclei, 2 plates somatosensory cortex Pvalb+ nuclei, 1 plate striatium Pvalb+ nuclei, 3 plates M2 cortex Pvalb+ nuclei, and 3 batches of Patch-seq samples. We used 96-well plates to collect and process nuclei for Smart-seq2 library construction.
Contributor(s) Levin JZ, Simmons SK, Fu Z, Li Y, Lopez VG, Adiconis X, Feng G
Citation(s) 32699411
Submission date Feb 13, 2020
Last update date Oct 27, 2020
Contact name Joshua Levin
Organization name Broad Institute
Department Stanley Center
Street address 75 Ames St
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (2)
GPL16417 Illumina MiSeq (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (3647)
GSM4310390 TRN1
GSM4310391 TRN2
GSM4310392 TRN3
BioProject PRJNA606580
SRA SRP249377

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Supplementary file Size Download File type/resource
GSE145273_TPM.TRN.tsv.gz 27.5 Mb (ftp)(http) TSV
GSE145273_TPM.nonTRN.tsv.gz 11.9 Mb (ftp)(http) TSV
GSE145273_TPM.patch.tsv.gz 1.9 Mb (ftp)(http) TSV
SRA Run SelectorHelp
Processed data are available on Series record
Raw data are available in SRA

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