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| Status |
Public on Aug 10, 2020 |
| Title |
Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Recent success in identifying gene regulatory elements in the context of recombinant adeno-associated virus vectors have enabled cell type-restricted gene expression. However, within the cerebral cortex these tools are presently limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple novel enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we identified enhancers that target the breadth of its expression, including two selective for parvalbumin and vasoactive intestinal peptide cortical interneurons. Demonstrating the functional utility of these elements, we found that the PV-specific enhancer allowed for the selective targeting and manipulation of fast-spiking cortical interneurons across species, from mice to humans.
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| Overall design |
scATAC library generated from Dlx6a-Cre;flox-Sun1-eGFP mouse primary visual cortex (V1) at P28 on the 10X Chromium platform.
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| Contributor(s) |
Allaway K, Saldi G, Dimidschstein J |
| Citation(s) |
32807948 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| UG3 MH120096 |
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species. |
THE BROAD INSTITUTE, INC. |
Jordane Dimidschstein |
| UG3 MH120096 |
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species. |
THE BROAD INSTITUTE, INC. |
GORDON J FISHELL |
| F31 NS103398 |
The Development and Diversity of Forebrain Cholinergic Neurons |
NEW YORK UNIVERSITY SCHOOL OF MEDICINE |
Kathryn Claire Allaway |
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| |
| Submission date |
Jun 15, 2020 |
| Last update date |
Nov 09, 2020 |
| Contact name |
Kathryn Allaway |
| Organization name |
Broad Institute
|
| Department |
Stanley Center for Psychiatric Disease
|
| Lab |
Fishell Lab
|
| Street address |
75 Ames St
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA639441 |
| SRA |
SRP267302 |
