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| Status |
Public on May 02, 2023 |
| Title |
Brain-wide Correspondence Between Neuronal Epigenomics and Long-Distance Projections |
| Project |
CEMBA Epigenomic Landscape of Mouse Brain
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| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Single-cell genetic and epigenetic analyses parse the brain’s billions of neurons into thousands of “cell-type” clusters, each residing in different brain structures. Many of these cell types mediate their unique functions by virtue of targeted long-distance axonal projections to allow interactions between specific cell types. Here we have used Epi-Retro-Seq to link single cell epigenomes and associated cell types to their long-distance projections for 33,034 neurons dissected from 32 different source regions projecting to 24 different targets (225 source→target combinations) across the whole mouse brain. We highlight uses of this large data set for interrogating both overarching principles relating projection cell types to their transcriptomic and epigenomic properties and for addressing and developing specific hypotheses about cell types and connections as they relate to genetics. We provide an overall synthesis of the data set with 926 statistical comparisons of the discriminability of neurons projecting to each target for every dissected source region. We integrate this dataset into the larger, annotated BICCN cell type atlas composed of millions of neurons to link projection cell types to consensus clusters. Integration with spatial transcriptomic data further assigns projection-enriched clusters to much smaller source regions than afforded by the original dissections. We exemplify these capabilities by presenting in-depth analyses of neurons with identified projections from the hypothalamus, thalamus, hindbrain, amygdala, and midbrain to provide new insights into the properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription factor binding motifs, and neurotransmitter usage.
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| Overall design |
In Epi-Retro-Seq, the retrograde viral tracer rAAV2-retro-Cre is injected in the target region in an INTACT mouse, turning on Cre-dependent nuclear-GFP expression in neurons that project to the injected target, throughout the mouse brain. The brain is then sectioned into eighteen 600-micron coronal slices, and the brain regions of interest are mannually dissected from each slice. Nuclei are sampled from 4 mice (2 male and 2 female) for each projection target. Nuclei from each of the dissected source regions are prepared, from which GFP+/NeuN+ nuclei (the GFP-labeled projection neurons) are isolated as single nuclei using fluorescence activated nuclei sorting (FANS) and assayed using snmC-Seq2/3 to profile their genome-wide DNA methylation signatures. Low-quality nuclei were removed.
This project includes the following series:
GSE150170 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150170
GSE230818 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE230818
GSE231230 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231230
GSE231326 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231326
GSE231414 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231414
GSE231442 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231442
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| Contributor(s) |
Zhou J, Zhang Z, Wu M, Liu H, Pang Y, Bartlett A, Rivkin AC, Lagos WN, Williams E, Lee C, Assakura Miyazaki P, Aldridge AI, Zeng Q, Salinda JA, Claffey N, Liem M, Fitzpatrick C, Boggeman L, Altshul J, Kenworthy MA, Valadon C, Nery JR, Castanon RG, Patne NS, Vu M, Rashid M, Jacobs MW, Ito-Cole T, Osteen J, Huang S, Pinto-Duartec A, Dominguez B, Smith JB, O'Connor C, Lee K, Mukamel EA, Jin X, Behrens MM, Ecker JR, Callaway EM |
| Citation(s) |
38092919 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| U19 MH114831 |
Center for Epigenomics of the Mouse Brain Atlas (CEMBA) |
THE SALK INSTITUTE FOR BIOLOGICAL STUDIES |
Joseph R Ecker |
| HHMI_Ecker_J |
Investigator |
Ecker, Joseph R. |
Joseph R. Ecker |
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| Submission date |
Apr 27, 2023 |
| Last update date |
Dec 15, 2023 |
| Contact name |
Joseph R Ecker |
| E-mail(s) |
ecker@salk.edu
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| Phone |
8584534100
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| Organization name |
HHMI-Salk-Institute
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| Department |
Genomic Analysis Laboratory
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| Lab |
Ecker lab
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| Street address |
10010 North Torrey Pines Road
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE230782_CEMBA.epiretro.mcds.tar.gz |
59.9 Gb |
(ftp)(http) |
TAR |
| Processed data provided as supplementary file |
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