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Status |
Public on Feb 24, 2021 |
Title |
RNA-seq analysis of mouse cDC1 and cDC2 populations upon DC-SCRIPT depletion |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of this lineage diversity, its genetic basis is not fully understood. DC-SCRIPT (Zfp366) is a poorly known transcription factor expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8-dependent conventional DC1 (cDC1), while cDC2 differentiated normally. The residual DC-SCRIPT-deficient cDC1s had impaired CD8+ T-cell cross-priming, which could be in part explained by the direct control of DC-SCRIPT on IL-12p40 production. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.
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Overall design |
cDC1s and cDC2s were sorted from the spleens of WT and Zfp366-/- mice. RNA was extracted and profiled using RNA-seq. Biological triplicates were prepared for each genotype to produce twelve samples in total.
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Contributor(s) |
Coughlan HD, Smyth GK |
Citation(s) |
33811060 |
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Submission date |
Jan 19, 2021 |
Last update date |
May 26, 2021 |
Contact name |
Gordon K Smyth |
E-mail(s) |
smyth@wehi.edu.au
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Phone |
(+61 3) 9345 2326
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Fax |
(+61 3) 9347 0852
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URL |
http://www.wehi.edu.au
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Organization name |
Walter and Eliza Hall Institute of Medical Research
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Department |
Bioinformatics
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Lab |
Smyth
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Street address |
1G Royal Pde
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City |
Parkville |
State/province |
Vic |
ZIP/Postal code |
3052 |
Country |
Australia |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (12)
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This SubSeries is part of SuperSeries: |
GSE165361 |
RNA-seq and CUT&Tag analysis of mouse cDC1 and cDC2 populations upon DC-SCRIPT depletion |
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Relations |
BioProject |
PRJNA693308 |
SRA |
SRP302432 |