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Series GSE215180 Query DataSets for GSE215180
Status Public on May 01, 2024
Title Selective requirement of 3D genomic organization for the Mdm1-Il22-Ifng locus regulation in initial Th1 cell lineage specification and differentiation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Eukaryotic DNA fibers are organized into structured subunits in the nucleus, but the extent to which these 3D chromatin architectures influence cytokine expression remains unclear. Here, we investigate the role of dynamic loop formation within the topologically associating domain (TAD) in regulating the expression of two critical cytokines, interferon-gamma (IFN-) and interleukin-22 (IL-22). These cytokine loci are closely located in the genome and are associated with complex enhancer landscapes, which are selectively active in type 1 and type 3 lymphocytes. Using in situ Hi-C, we demonstrate inducible TADs that insulate Ifng and Il22 enhancers during Th1 differentiation. Deleting the boundary of these TADs resulted in imbalanced Th1- and Th17-associated immunity, both in vitro and in vivo. In contrast, this boundary element was dispensable for cytokine regulation in NK cells. Our finding suggest that precise cytokine regulation relies on lineage- and developmental stage-specific interactions of 3D chromatin architectures and enhancer landscapes.
Overall design We differentiate naive T cells with TCR signaling CD3 and CD28 and cytokines IL-12 ex vivo to Th1 cells in WT and IfngCTCFdel mice, and performed focused Hi-C for 3-D architecture and chromatin interactions, bulk RNA-seq for transcriptomic analysis, in parellel using ATAC-seq and ChIP-seq (p300, rad21, CTCF, H3K4me1, H3K27ac, H3K4me3) for epigenomic profiling. To understand the immune response change in the WT and IfngCTCFdel mice in vivo, we measured gene expression of cells isolated from mice infected by Toxoplasma gondii for three and seven days, and by LCMV for 4 days and 7 days using single cell RNA-seq. We also used whole genome sequencing to evaluate of our mouse model generated by CRISPR/Cas9.
Contributor(s) Liu C, Nagashima H, Fernando N, Bass V, Gopalakrishnan J, Signorella S, Montgomery W, Lim A, Harrison O, Reich L, Yao C, Sun H, Brooks S, Kan J, Nagarajan V, Zhao Y, Jung S, Phillips R, Mikami Y, Lareau CA, Kanno Y, Jankovic D, Aryee M, Pekowska A, Belkaid Y, O’Shea J, Shih H
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Submission date Oct 10, 2022
Last update date May 01, 2024
Contact name Vijay Nagarajan
Organization name National Institutes Of Health
Department National Eye Institute
Lab Laboratory of Immunology
Street address 10 Center Drive, 10/10N248
City Bethesda
State/province Maryland
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (20)
GSM6625282 scRNA_WT_Pec_NK_Toxo_day3
GSM6625283 scRNA_WT_Pec_Th1_Toxo_day3
GSM6625284 scRNA_KO_Pec_NK_Toxo_day3
This SubSeries is part of SuperSeries:
GSE215181 Selective requirement of 3D genomic organization for the Mdm1-Il22-Ifng locus regulation in initial Th1 cell lineage specification and differentiation
BioProject PRJNA889043

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Supplementary file Size Download File type/resource
GSE215180_RAW.tar 292.2 Mb (http)(custom) TAR (of H5)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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