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| Status |
Public on Dec 20, 2023 |
| Title |
Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease which targets mature oligodendrocytes (MOLs) and their myelin. MOLs are transcriptionally heterogeneous, and can transition to immune-like states in the context of MS. However, the intricacies of their dynamics throughout disease progression remain poorly understood. Here, we employed simultaneous single-cell multiome ATAC and RNA sequencing targeting oligodendroglia (OLGs) from the experimental autoimmune encephalomyelitis (EAE) MS mouse model, at different stages of the disease course. We found that the transition to immune OLGs states occurs already at early stages of EAE and these persist at late stages of the disease. Interestingly, transcription factor activity suggested immunosuppression activity in MOLs at early stages of EAE and we also observed a transitory activation of a regenerative programme in MOLs at this stage. Importantly, different MOLs present a differential responsiveness to EAE, with MOL2 exhibiting stronger transcriptional immune response than MOL5/6. Moreover, we observed divergence responses at the epigenetic level of MOL2 and MOL5/6 during disease evolution. Thus, our single-cell multiomic resource highlights dynamic and distinct responses of OLG subpopulations to the evolving environment in EAE, which might modulate their response to regenerative therapeutic interventions in MS.
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| Overall design |
Sox10:Cre-RCE:LoxP mice are a strain of mice obtained originally by crossing mice with Cre recombinase under the control of the Sox10 promoter with reporter mice RCE:loxP-EGFP to label the complete oligodendrocyte (OL) lineage
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| Web link |
https://doi.org/10.1101/2023.12.18.572120
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| Contributor(s) |
Zheng C, Hervé B, Meijer M, Rubio Rodriguez-Kirby LA, Ortlieb Guerreiro Cacais A, Kukanja P, Kabbe M, Olsson T, Agirre E, Castelo-Branco G |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 19, 2023 |
| Last update date |
Mar 20, 2024 |
| Contact name |
Bastien Hervé |
| E-mail(s) |
bastienherve61@gmail.com
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| Organization name |
Karolinska Institutet
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| Department |
MBB
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| Lab |
Castelo-Branco
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| Street address |
Solnavägen 9
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| City |
Solna |
| ZIP/Postal code |
17165 |
| Country |
Sweden |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (38)
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| GSM7982311 |
Early, EAE, replicate2, scATACseq |
| GSM7982312 |
Early, EAE, replicate3, scRNAseq |
| GSM7982313 |
Early, EAE, replicate3, scATACseq |
| GSM7982314 |
Early, EAE, replicate4, scRNAseq |
| GSM7982315 |
Early, EAE, replicate4, scATACseq |
| GSM7982316 |
Peak, EAE, replicate1, scRNAseq |
| GSM7982317 |
Peak, EAE, replicate1, scATACseq |
| GSM7982318 |
Peak, EAE, replicate2, scRNAseq |
| GSM7982319 |
Peak, EAE, replicate2, scATACseq |
| GSM7982320 |
Peak, EAE, replicate3, scRNAseq |
| GSM7982321 |
Peak, EAE, replicate3, scATACseq |
| GSM7982322 |
Peak, EAE, replicate4, scRNAseq |
| GSM7982323 |
Peak, EAE, replicate4, scATACseq |
| GSM7982324 |
Late, EAE, replicate1, scRNAseq |
| GSM7982325 |
Late, EAE, replicate1, scATACseq |
| GSM7982326 |
Late, EAE, replicate2, scRNAseq |
| GSM7982327 |
Late, EAE, replicate2, scATACseq |
| GSM7982328 |
Late, EAE, replicate3, scRNAseq |
| GSM7982329 |
Late, EAE, replicate3, scATACseq |
| GSM7982330 |
Late, EAE, replicate4, scRNAseq |
| GSM7982331 |
Late, EAE, replicate4, scATACseq |
| GSM7982332 |
Late, EAE, replicate5, scRNAseq |
| GSM7982333 |
Late, EAE, replicate5, scATACseq |
| GSM7982334 |
Peak, Ctrl, replicate1, scRNAseq |
| GSM7982335 |
Peak, Ctrl, replicate1, scATACseq |
| GSM7982336 |
Early, Ctrl, replicate1, scRNAseq |
| GSM7982337 |
Early, Ctrl, replicate1, scATACseq |
| GSM7982338 |
Peak, Ctrl, replicate2, scRNAseq |
| GSM7982339 |
Peak, Ctrl, replicate2, scATACseq |
| GSM7982340 |
Early, Ctrl, replicate2, scRNAseq |
| GSM7982341 |
Early, Ctrl, replicate2, scATACseq |
| GSM7982342 |
Late, Ctrl, replicate1, scRNAseq |
| GSM7982343 |
Late, Ctrl, replicate1, scATACseq |
| GSM7982344 |
Late, Ctrl, replicate2, scRNAseq |
| GSM7982345 |
Late, Ctrl, replicate2, scATACseq |
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| Relations |
| BioProject |
PRJNA1054583 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE250589_Astro_Ctrl-TileSize-100-normMethod-rc.bw |
80.2 Mb |
(ftp)(http) |
BW |
| GSE250589_Astro_Early-TileSize-100-normMethod-rc.bw |
38.4 Mb |
(ftp)(http) |
BW |
| GSE250589_Astro_Late-TileSize-100-normMethod-rc.bw |
5.3 Mb |
(ftp)(http) |
BW |
| GSE250589_Astro_Peak-TileSize-100-normMethod-rc.bw |
4.3 Mb |
(ftp)(http) |
BW |
| GSE250589_COP_Ctrl-TileSize-100-normMethod-rc.bw |
1.6 Mb |
(ftp)(http) |
BW |
| GSE250589_COP_Late-TileSize-100-normMethod-rc.bw |
36.8 Mb |
(ftp)(http) |
BW |
| GSE250589_COP_Peak-TileSize-100-normMethod-rc.bw |
11.3 Mb |
(ftp)(http) |
BW |
| GSE250589_EAE_multiomics.bedpe.gz |
8.5 Mb |
(ftp)(http) |
BEDPE |
| GSE250589_EAE_multiomics.rds.gz |
10.7 Gb |
(ftp)(http) |
RDS |
| GSE250589_EAE_multiomics_fragments.tsv.gz |
16.2 Gb |
(ftp)(http) |
TSV |
| GSE250589_MOL1_Ctrl-TileSize-100-normMethod-rc.bw |
11.7 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL1_Early-TileSize-100-normMethod-rc.bw |
3.2 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL1_Late-TileSize-100-normMethod-rc.bw |
31.3 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL1_Peak-TileSize-100-normMethod-rc.bw |
2.0 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL2_Ctrl-TileSize-100-normMethod-rc.bw |
10.4 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL2_Early-TileSize-100-normMethod-rc.bw |
45.1 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL2_Late-TileSize-100-normMethod-rc.bw |
100.3 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL2_Peak-TileSize-100-normMethod-rc.bw |
99.3 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL56_Ctrl-TileSize-100-normMethod-rc.bw |
103.4 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL56_Early-TileSize-100-normMethod-rc.bw |
84.9 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL56_Late-TileSize-100-normMethod-rc.bw |
79.6 Mb |
(ftp)(http) |
BW |
| GSE250589_MOL56_Peak-TileSize-100-normMethod-rc.bw |
43.0 Mb |
(ftp)(http) |
BW |
| GSE250589_Micro_Ctrl-TileSize-100-normMethod-rc.bw |
17.3 Mb |
(ftp)(http) |
BW |
| GSE250589_Micro_Early-TileSize-100-normMethod-rc.bw |
16.8 Mb |
(ftp)(http) |
BW |
| GSE250589_Micro_Late-TileSize-100-normMethod-rc.bw |
44.9 Mb |
(ftp)(http) |
BW |
| GSE250589_Micro_Peak-TileSize-100-normMethod-rc.bw |
35.7 Mb |
(ftp)(http) |
BW |
| GSE250589_OPC_Ctrl-TileSize-100-normMethod-rc.bw |
7.5 Mb |
(ftp)(http) |
BW |
| GSE250589_OPC_Early-TileSize-100-normMethod-rc.bw |
3.1 Mb |
(ftp)(http) |
BW |
| GSE250589_OPC_Late-TileSize-100-normMethod-rc.bw |
36.4 Mb |
(ftp)(http) |
BW |
| GSE250589_OPC_Peak-TileSize-100-normMethod-rc.bw |
29.6 Mb |
(ftp)(http) |
BW |
| GSE250589_RAW.tar |
19.6 Gb |
(http)(custom) |
TAR (of H5, TBI, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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