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Series GSE62704 Query DataSets for GSE62704
Status Public on Dec 14, 2014
Title A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin states (RNA-Seq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into distinct cell fates are not fully understood. Here, we identify chromatin-regulating and cell-fate-determining transcription factors (TF) governing dendritic cell (DC) development by annotating the enhancer and promoter landscapes of the DC lineage. Combining these analyses with detailed over-expression, knockdown and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, differential activity of TF can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes.
Overall design Here analyzed 2 experiments, each one contains samples of moDC and pDC ex vivo cultured cells. The first experiment contains 32 samples of moDC and pDC following stimulation with various TLR stimulators. The second experiment contains 8 samples of moDC and pDC following perturbations; Cebpb and Irf8 knock down or over expression.
Citation(s) 25453760
Submission date Oct 24, 2014
Last update date May 15, 2019
Contact name Ido Amit
Phone 972-8-9343338
Organization name Weizmann Institute of Science
Department Immunology
Street address 234 Herzl st.
City Rehovot
ZIP/Postal code 760001
Country Israel
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (48)
GSM1531752 moDC_NT
GSM1531753 moDC_1 hour LPS
GSM1531754 moDC_2 hour LPS
BioProject PRJNA264837
SRA SRP049257

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Supplementary file Size Download File type/resource
GSE62704_TLRs_stimulated_moDC_and_pDC.xlsx 3.0 Mb (ftp)(http) XLSX
GSE62704_hematopoietic_cells_expression.xlsx 1008.1 Kb (ftp)(http) XLSX
GSE62704_moDC_and_pDC_Genes_perturbation.xlsx 499.6 Kb (ftp)(http) XLSX
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