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Status |
Public on May 01, 2016 |
Title |
The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2 |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Plasmacytoid dendritic cells (pDCs) develop from pre-pDCs, while two lineages of conventional DCs (cDC1s and cDC2s) develop from lineage-committed pre-cDCs. A number of transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2, Id2) and cDC1s (IRF8, Id2 and Batf3) however, those required for the early commitment of pre-cDCs towards the cDC2 lineage are unknown. Here we identified the TF Zinc finger E box binding homeobox 2 (Zeb2), to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onwards, and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c+ cells had a cell intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c+ cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was upregulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 ChIP analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.
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Overall design |
cDC1s and cDC2s were isolated and sorted from spleens of CD11cCRExZeb2fl/fl, CD11cCRExR26-Zeb2Tg/Tg or CRE- littermate controls. 24 samples (RNA-Seq) in total. RNA was isolated, amplified by SMARTer amplification, converted to cDNA and then sequenced using Illumina NextSeq.
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Contributor(s) |
Scott CL, Soen B, Martens L, Skrypek N, Saelens W, Taminau J, Blancke G, Van Isterdael G, Huylebroeck D, Haigh J, Saeys Y, Guilliams M, Lambrecht BN, Berx G |
Citation(s) |
27185854 |
Submission date |
Apr 04, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Liesbet Martens |
E-mail(s) |
liesbet.martens@irc.vib-ugent.be
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Organization name |
VIB-University of Ghent
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Department |
VIB Inflammation Research Center
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Street address |
Technologiepark 927
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City |
Zwijnaarde |
ZIP/Postal code |
9052 |
Country |
Belgium |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (24)
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Relations |
BioProject |
PRJNA317353 |
SRA |
SRP072845 |
Supplementary file |
Size |
Download |
File type/resource |
GSE79903_RAW.tar |
2.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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