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| Status |
Public on Oct 26, 2023 |
| Title |
Transcriptomic atlas of midbrain dopamine neurons uncovers differential vulnerability in a Parkinsonism lesion model |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Midbrain dopamine (mDA) neurons comprise a diverse group of cells with unique innervation targets and functions. This is illustrated by the selective sensitivity of mDA neurons of the substantia nigra compacta (SNc) in patients with Parkinson’s disease, while those in the ventral tegmental area (VTA) are relatively spared. Here we used single nuclei RNA sequencing (snRNA-seq) of approximately 70,000 mouse midbrain cells to build a high-resolution atlas of mouse mDA neuron diversity at the molecular level. The results showed that differences between mDA neuron groups could best be understood as a continuum without sharp differences between subtypes. Thus, we assigned mDA neurons to several “territories” and “neighborhoods” within a shifting gene expression landscape where boundaries are gradual rather than discrete. Based on the enriched gene expression patterns of these territories and neighborhoods, we were able to localize them in the adult mouse midbrain. Moreover, because the underlying mechanisms for the variable sensitivities of diverse mDA neurons to pathological insults are not well understood, we analyzed surviving neurons after partial 6-hydroxydopamine (6-OHDA) lesions to unravel gene expression patterns that correlate with mDA neuron vulnerability and resilience. Together, this atlas provides a basis for further studies on the neurophysiological role of mDA neurons in health and disease.
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| Overall design |
Molecular charachterization of midbrain dopamine neurons in untreated, unlesioned (intact) and partial 6-hydroxydopamine (6-OHDA) lesioned conditions using single nuclei RNA sequencing.
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| Contributor(s) |
Yaghmaeian-Salmani B, Lahti L, Gillberg L, Jacobsen JK, Mantas I, Svenningsson P, Perlmann T |
| Citation(s) |
38587883 |
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| Submission date |
May 31, 2023 |
| Last update date |
Apr 09, 2024 |
| Contact name |
Behzad Yaghmaeian Salmani |
| E-mail(s) |
behzad.yaghmaeian.salmani@ki.se
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| Phone |
0723505234
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| Organization name |
Karolinska Institute
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| Department |
CMB
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| Street address |
Department of Cell and Molecular Biology (CMB) Karolinska Institute,, Biomedicum, Solnavägen 9, Solna, Stockholm, P.O. Box 285 SE-171 77 Stockholm, Sweden
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| City |
Stockholm |
| State/province |
Solna, Stockholm |
| ZIP/Postal code |
SE-171 77 |
| Country |
Sweden |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (18)
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| GSM7438334 |
untreated, 10X_19_009 |
| GSM7438335 |
untreated, 10X_19_010 |
| GSM7438336 |
untreated, 10X_19_011 |
| GSM7438337 |
lesioned, P18856_3001 |
| GSM7438338 |
intact, P18856_3002 |
| GSM7438339 |
lesioned, P18856_3003 |
| GSM7438340 |
intact, P18856_3004 |
| GSM7438341 |
lesioned, P18856_3005 |
| GSM7438342 |
intact, P18856_3006 |
| GSM7438343 |
lesioned, P18856_3007 |
| GSM7438344 |
intact, P18856_3008 |
| GSM7438345 |
lesioned, P18856_3009 |
| GSM7438346 |
intact, P18856_3010 |
| GSM7438347 |
lesioned, P18856_3011 |
| GSM7438348 |
intact, P18856_3012 |
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| Relations |
| BioProject |
PRJNA978334 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE233866_lesion_intact_counts.csv.gz |
282.7 Mb |
(ftp)(http) |
CSV |
| GSE233866_untreated_counts.csv.gz |
31.5 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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