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| Status |
Public on Apr 14, 2026 |
| Title |
Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Activation of dendritic cells (DCs) is linked to increased glycolysis. However, the role of the mitochondrial electron transport chain (ETC) in conventional DC subset function is poorly defined. Here, we revealed that immunogenic activation elevates late oxygen consumption in cDC1s, but not cDC2s. To investigate the relevance of the ETC in DC immunogenicity, we generated mice with impaired ETC complex III function in DCs. ETC complex III impairment attenuated poised or adjuvant-triggered cDC1 activation, migration and capability to prime T cells for anti-cancer immunity, while it had a mild effect on cDC2s. Mechanistically, loss of complex III in cDC1s led to a deregulated redox and metabolite balance causing DNA hypermethylation of PU.1-binding regions. This DNA hypermethylation diminished early stimulus-induced gene expression linked to immunogenic responsiveness of cDC1s, which was rescued via ectopic expression of alternative oxidase. Our findings show how the ETC differentially regulates the immunogenic function of cDC subsets.
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| Overall design |
50 ug poly(I:C) LMW and 50 ug R848 or the control PBS were intravenously administered into Uqcrqf/f or Itgax-Uqcrqf/f mice and, after 1.5 hours, the spleen was harvested and processed. CD8+ cDC1 and CD11b+ cDC2 were FACS sorted, the RNA extracted and used for RNA sequencing.
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| Contributor(s) |
Heras-Murillo I, Wculek SK, Sancho D |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 29, 2024 |
| Last update date |
Apr 14, 2026 |
| Contact name |
Ignacio Heras-Murillo |
| E-mail(s) |
iheras@cnic.es
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| Organization name |
CNIC
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| Street address |
c/Melchor Fernandez Almagro, 3
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| City |
MADRID |
| State/province |
MADRID |
| ZIP/Postal code |
28029 |
| Country |
Spain |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (24)
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| GSM8489672 |
CD8+ cDC1, Uqcrqf/f, PBS, rep1 |
| GSM8489673 |
CD8+ cDC1, Uqcrqf/f, polyI:C+R848, 1.5h, rep1 |
| GSM8489674 |
CD8+ cDC1, Itgax-Uqcrqf/f, PBS, rep1 |
| GSM8489675 |
CD8+ cDC1, Itgax-Uqcrqf/f, polyI:C+R848, 1.5h, rep1 |
| GSM8489676 |
CD11b+ cDC2, Uqcrqf/f, PBS, rep1 |
| GSM8489677 |
CD11b+ cDC2, Uqcrqf/f, polyI:C+R848, 1.5h, rep1 |
| GSM8489678 |
CD11b+ cDC2,Itgax-Uqcrqf/f, PBS, rep1 |
| GSM8489679 |
CD11b+ cDC2, Itgax-Uqcrqf/f, polyI:C+R848, 1.5h, rep1 |
| GSM8489680 |
CD8+ cDC1, Uqcrqf/f, PBS, rep2 |
| GSM8489681 |
CD8+ cDC1, Uqcrqf/f, polyI:C+R848, 1.5h, rep2 |
| GSM8489682 |
CD8+ cDC1, Itgax-Uqcrqf/f, PBS, rep2 |
| GSM8489683 |
CD8+ cDC1, Itgax-Uqcrqf/f, polyI:C+R848, 1.5h, rep2 |
| GSM8489684 |
CD11b+ cDC2, Uqcrqf/f, PBS, rep2 |
| GSM8489685 |
CD11b+ cDC2, Uqcrqf/f, polyI:C+R848, 1.5h, rep2 |
| GSM8489686 |
CD11b+ cDC2, Itgax-Uqcrqf/f, PBS, rep2 |
| GSM8489687 |
CD11b+ cDC2, Itgax-Uqcrqf/f, polyI:C+R848, 1.5h, rep2 |
| GSM8489688 |
CD8+ cDC1, Uqcrqf/f, PBS, rep3 |
| GSM8489689 |
CD8+ cDC1, Uqcrqf/f, polyI:C+R848, 1.5h, rep3 |
| GSM8489690 |
CD8+ cDC1, Itgax-Uqcrqf/f, PBS, rep3 |
| GSM8489691 |
CD8+ cDC1, Itgax-Uqcrqf/f, polyI:C+R848, 1.5h, rep3 |
| GSM8489692 |
CD11b+ cDC2, Uqcrqf/f, PBS, rep3 |
| GSM8489693 |
CD11b+ cDC2, Uqcrqf/f, polyI:C+R848, 1.5h, rep3 |
| GSM8489694 |
CD11b+ cDC2, Itgax-Uqcrqf/f, PBS, rep3 |
| GSM8489695 |
CD11b+ cDC2, Itgax-Uqcrqf/f, polyI:C+R848, 1.5h, rep3 |
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| Relations |
| BioProject |
PRJNA1154295 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE276024_NormCounts.txt.gz |
2.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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