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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| 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.
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| Contributor(s) |
Levin JZ, Simmons SK, Fu Z, Li Y, Lopez VG, Adiconis X, Feng G |
| Citation(s) |
32699411 |
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| Submission date |
Feb 13, 2020 |
| Last update date |
Oct 27, 2020 |
| Contact name |
Joshua Levin |
| E-mail(s) |
jlevin@broadinstitute.org
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| Organization name |
Broad Institute
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| Department |
Stanley Center
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| Street address |
75 Ames St
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (2) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (3647)
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| Relations |
| BioProject |
PRJNA606580 |
| SRA |
SRP249377 |
| 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 Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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