Project description:Loss-of-function mutations have provided crucial insights into the immunoregulatory actions of Foxp3+ regulatory T cells (Tregs). By contrast, we know very little about the consequences of defects that amplify aspects of Treg function or differentiation. We report that mice heterozygous for an Ikbkb gain-of-function (GoF) mutation develop psoriasis. Doubling the gene dose (IkbkbGoF/GoF) results in dactylitis, spondylitis, and characteristic nail changes, which are features of psoriatic arthritis. IkbkbGoF mice exhibit a selective expansion of Foxp3+ CD25+ Tregs of which a subset express IL-17. These modified Tregs were enriched at the inflamed tissues and spleen, and their transfer was sufficient to induce disease without conventional T cells. Single-cell transcriptional and phenotyping analyses of isolated Tregs revealed expansion of non-lymphoid tissue (tissue-resident) Tregs expressing Th17-related genes, Helios, tissue-resident markers including CD103 and CD69, and a prominent NF-kB transcriptome. Thus, IKK2 regulates tissue-resident Treg differentiation, and overactivity drives dose-dependent skin and systemic inflammation.
Project description:We report gene expression changes between SEC23B WT and MUT cells after treatment with Tunicamycin. The overall goal is to agnostically determine impacted signaling pathways in the wildtype and mutant settings.
Project description:Elf5 induced transcriptional changes in MDA-MB-231 origin, control (mut Elf5) vs WT ELF5 Two-condition experiment, control (mut-Elf5) vs WT-Elf5. Each has 3 biological repeats.
Project description:Transcriptional profiling of FACS-sorted ureteric bud-derivative cells from Hoxb7CreGFP mice without floxed Bdkrb2 allele (WT) or with homozygously floxed Bdkrb2 alleles (MUT) at the age of postnatal one. Both WT and MUT mice have R26RTdTomato allele as a recombinase efficiency indicator, which allows the FACS to sort cells according to both GFP and TdTomato. This experiment aimed to uncover the genome-wide alternation in gene expression resulting from the removal of Bdkrb2 in the ureteric buds and their derivative collecting ducts.
Project description:Cognate antigen signals control CD8+ T cell priming, expansion size and effector versus memory cell fates, however, it is not clear whether they can also modulate the functional features of memory CD8+ T cells. We observed that OT-I cells that were primed with weak cognate antigen signals incorporate more cytokine signals, leading to a hypothesis that CD8+ T cells that receive weak TCR signals require cytokine signals to form functional memory. Using a previously described mouse model in which IL-2 signaling via its high affinity receptor CD25 is selectively impaired, the “Il2ramut/mut” mouse, we conducted a comparative analysis of gene expression and epigenetic landscape of Il2ramut/mut and WT OT-I memory cells that were primed with strong (Lm-Ova N4) versus weak (Lm-Ova T4). RNA seq data showed that both TCR and IL-2 priming signals have minimal effect on gene expression in resting memory CD8 T cells, but they significantly modify the epigenetic landscape of the memory CD8 T cells. These findings have important contributions to the current understanding of how priming signals program memory CD8 T cells in vivo.
Project description:MeRIP-Seq data aligned to the genome (GRCh38) for cells with IDH1-Mut or IDH1-WT genotypes. Aligned data (BAM) are separated into input RNA and m6A immunoprecipitated RNA for each cell sample.