Transcriptome analysis of Regnase-1 deficient B cells at steady-state or upon B cell receptor stimulation
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ABSTRACT:
PROVIDER: PRJNA616414 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11453500.fastq.gz | Fastqsanger.gz | |||
| SRR11453501.fastq.gz | Fastqsanger.gz | |||
| SRR11453502.fastq.gz | Fastqsanger.gz | |||
| SRR11453503.fastq.gz | Fastqsanger.gz | |||
| SRR11453504.fastq.gz | Fastqsanger.gz |
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Project description:This study aims to identify the transcriptional programs that are regulated by the RNA binding protein Regnase-1 in B cells. To address the B cell specific roles of Regnase-1, we performed RNA seq analysis of B cells isolated from the spleens of mice in which Regnase-1 was deleted in a B cell specific manner using an inducible cre recombinase model, referred to as Regnase-1f/f hCD20TamCre, and compared to the appropriate controls, referred to as Regnase-1+/+ hCD20TamCre. Determining the differentially expressed genes from Regnase-1 deficient B cells compared to the control cells enabled identification of the transcriptional program regulated by Regnase-1 in B cells during steady state. In addition, we analyzed Regnase-1 deficient and control B cells that were stimulated with a stimulatory anti-IgM F(ab’)2 antibody that engages the B cell receptor (BCR). BCR engagement results into activation of B cells. Therefore, the differentially expressed genes from this analysis enabled identification of the genes that are modulated by Regnase-1 in B cells during an activated state.
2021-03-01 | GSE147799 | GEO
Project description:Having identified the crucial role of IFN-γ in anti-tumor immunity of Reg-1ΔNK, we attempted to elucidate the mechanism underlying the regulation of Ifng in the context of Regnase-1 deletion. Despite the notable increase in Ifng mRNA expression in Reg-1ΔNK-NK cells, Ifng was not a direct substrate of Regnase-1. However, the production of the IFN-γ was further enhanced upon stimulation with IL-12/18. We proposed that modifications may have occurred in the transcriptional regulation of Ifng in Reg-1ΔNK-NK cells.
2024-05-30 | GSE237641 | GEO
Project description:Having identified the crucial role of IFN-γ in anti-tumor immunity of Reg-1ΔNK, we attempted to elucidate the mechanism underlying the regulation of Ifng in the context of Regnase-1 deletion. Despite the notable increase in Ifng mRNA expression in Reg-1ΔNK-NK cells, Ifng was not a direct substrate of Regnase-1. However, the production of the IFN-γ was further enhanced upon stimulation with IL-12/18. We proposed that modifications may have occurred in the transcriptional regulation of Ifng in Reg-1ΔNK-NK cells.
2024-05-30 | GSE237637 | GEO
Project description:Post-transcriptional regulation of immune-related transcripts by RNA-binding proteins (RBPs) impacts immune cell responses, including mast cell functionality. Despite their importance in immune regulation, the functional role of most RBPs remains to be understood. By manipulating the expression of specific RBPs in murine mast cells, coupled with mass spectrometry and transcriptomic analyses, we found that the Regnase family of proteins acts as a potent regulator of mast cell physiology. Specifically, Regnase-1 is required to maintain basic cell proliferation and survival, while both Regnase-1 and -3 cooperatively regulate the expression of inflammatory transcripts upon activation, with Tnf being a primary target in both human and mouse cells. Further, Regnase-3 directly interacts with Regnase-1 in mast cells and is necessary to restrain Regnase-1 expression through the destabilization of its transcript. Overall, our study identifies protein interactors of endogenously expressed Regnase factors, characterizes the regulatory interplay between Regnase family members in mast cells, and establishes their role in the control of mast cell homeostasis and inflammatory responses.
2024-05-31 | PXD051849 | Pride
Project description:The RNase Regnase-1 is a master RNA regulator in macrophages and T cells that degrades cellular and viral RNA upon NF-kB signaling. The roles of the other Regnase family-members remain largely unknown. Here, we analyze Regnase-3 deficient mice, which develop hypertrophic lymph nodes. We used various mice with immune cell specific deletions of Regnase-3 to demonstrate that Regnase-3 acts specifically within myeloid cells. Regnase-3 deficiency systemically increased interferon signaling, which increased the proportion of immature B and innate immune cells and suppressed follicles and germinal center formation. Expression analysis revealed that Regnase-3 and Regnase-1 share protein degradation pathways. Nevertheless, Regnase-3 expression is specifically high in macrophages and transcriptionally controlled by interferon signaling. Although direct targets in macrophages remain unknown, Regnase-3 can bind, degrade and regulate mRNAs, such Zc3h12a encoding Regnase-1, in vitro. These data indicate that Regnase-3, like Regnase-1, is an RNase and essential for immune homeostasis, but has diverged as a key regulator for the interferon pathway in macrophages.
2019-04-05 | GSE129325 | GEO
Project description:Dysregulation of mast cell activation can lead to allergic and anaphylactic reactions. Post-transcriptional regulation of immune-related transcripts by RNA-binding proteins (RBPs) is critical in controlling immune cell responses, including mast cell functionality. The Regnase family of RBPs plays a central role in regulating gene expression and controlling immune responses in both lymphoid and myeloid cells. However, what is the functional role of Regnase proteins in mast cells remains to be understood. Using different approaches of Regnase proteins depletion and deletion as well as overexpression by mRNA delivery, we found that Regnase-1 is a powerful negative regulator of mast cell proliferation, survival and ability to produce inflammatory cytokines. On the other hand, Regnase-3 was essential to modulate Regnase-1 expression in mast cells by direct targeting of the 3’-untranslated region of Regnase-1, leading to the destabilization of the Zc3h12a mRNA. Regnase-1 deletion had widespread effect on mast proliferation and survival even in the absence of stimulation and was at least in part linked to specific nuclear functions of Regnase-1 in modulating the ability of mast cells to withstand DNA damage. Overall, we describe the importance of Regnase proteins in modulating mast cell homeostatic and inflammatory responses and we describe the impact of Regnase-1 in the maintenance of genome stability.
2024-05-31 | GSE240095 | GEO
Project description:Dysregulation of mast cell activation can lead to allergic and anaphylactic reactions. Post-transcriptional regulation of immune-related transcripts by RNA-binding proteins (RBPs) is critical in controlling immune cell responses, including mast cell functionality. The Regnase family of RBPs plays a central role in regulating gene expression and controlling immune responses in both lymphoid and myeloid cells. However, what is the functional role of Regnase proteins in mast cells remains to be understood. Using different approaches of Regnase proteins depletion and deletion as well as overexpression by mRNA delivery, we found that Regnase-1 is a powerful negative regulator of mast cell proliferation, survival and ability to produce inflammatory cytokines. On the other hand, Regnase-3 was essential to modulate Regnase-1 expression in mast cells by direct targeting of the 3’-untranslated region of Regnase-1, leading to the destabilization of the Zc3h12a mRNA. Regnase-1 deletion had widespread effect on mast proliferation and survival even in the absence of stimulation and was at least in part linked to specific nuclear functions of Regnase-1 in modulating the ability of mast cells to withstand DNA damage. Overall, we describe the importance of Regnase proteins in modulating mast cell homeostatic and inflammatory responses and we describe the impact of Regnase-1 in the maintenance of genome stability.
2024-05-31 | GSE240035 | GEO
Project description:In this study, we exploited interactome-based approach to isolate Regnase-1 protein complexes and found that TLR-ligand, IL-1β, or IL-17 stimulation induces formation of the Regnase-1-14-3-3 or -βTRCP complex in a mutually exclusive manner.
2021-10-12 | PXD026561 | JPOST Repository
Project description:Regulation of lineage biases in hematopoietic stem and progenitor cells (HSPCs) is pivotal for balanced hematopoietic output. However, little is known about the mechanism behind lineage choice in HSPCs. Here, we show that mRNA decay factors Regnase-1 (Zc3h12a) and Regnase-3 (Zc3h12c) are critical for induction of myeloid lineage priming, restricting lymphoid differentiation in HSPCs. Regnase-1- and Regnase-3-mediated control of mRNA encoding Nfkbiz, a transcriptional and epigenetic regulator, was essential for balancing lymphoid/myeloid lineage output in HSPCs in vivo. Furthermore, single cell-assay for transposase-accessible chromatin sequencing (scATAC-seq) analysis revealed that Regnase-1 and Regnase-3 control the epigenetic landscape on myeloid-related gene loci in hematopoietic stem cells (HSCs) via Nfkbiz. Consistently, an antisense oligonucleotide designed to inhibit Regnase-1- and Regnase-3-mediated Nfkbiz mRNA degradation primed HSCs toward myeloid lineages by enhancing Nfkbiz expression. Collectively, the collaboration between post-transcriptional control and chromatin remodeling by the Regnase-1/Regnase-3-Nfkbiz axis governs lineage priming, instructing HSC lineage specification.
2024-02-09 | GSE228923 | GEO
Project description:Abstract Two major dendritic cell (DC) subsets have been described in the islets of mice: The immunogenic CD8α-CD11b+ DCs and the tolerogenic CD8α+CD103+ DCs. We have recently reported on reduced numbers of the minor population of tolerogenic CD8α+CD103+ DCs in the pancreas of 5 week old pre-diabetic non-obese diabetic (NOD) mice. Aim: To analyze also the larger subset of CD11c+CD8α- DCs isolated from the pancreas of pre-diabetic NOD mice 1) for maturation and tolerance inducing molecules found abnormally expressed on CD8α+CD103+ DCs, and 2) for genome-wide gene expression to further elucidate abnormalities in underlying gene expression networks. Methods: CD11c+CD8α- DCs were isolated from 5 week old C57BL/6 and NOD pancreas. Expression of cell surface markers including CD86, CCR5, CD11b, CD103, Clec9a, CD24 and CD200R3 were measured by FACS. Genome-wide gene expression by microarray was assessed during the steady state and after in vitro LPS stimulation. Results: The steady state pancreatic CD11c+ CD8α- DCs during the pre-diabetic stage showed: 1) A reduced expression of several gene networks important for the prime functions of the cell, such as for cell renewal, immune stimulation and immune tolerance induction, for migration and for the provision of growth factors for beta cell regeneration. This general deficiency state was corroborated by a reduced in vivo proliferation (BrdU incorporation) of the cells and the reduced expression in FACS analysis of CD86, CCR5, CD103, Clec9a, CD24 and CD200R3 on the cells. 2) A hyper reactivity of these cells to LPS correlated with an enhanced pro-inflammatory state characterized by altered expression of a number of classical pro-inflammatory factors and cytokines. Conclusion: The NOD CD11c+CD8α- DCs seem to be Janus-faced depending on the conditions: Deficient in steady state with reduced immune stimulation capabilities also for tolerance induction; over-inflammatory with a molecular profile suggesting a preferential stimulatory capacity for Th1 cells when encountering a Pathogen-Associated Molecular Pattern (PAMP) in the form of LPS. We used microarray gene expression analysis to explain the abnormal expression of several cell surface markers involved in tolerace, migration and maturation in the steady-state and to measure the effect of a PAMP such as LPS We isolated RNA from FACS sorted CD11c+CD8α- DCs in 10 pooled pancreases from pre-diabetic NOD and non-diabetic C57BL/6 mice at 5 weeks. In addition, we treated in another experiment the isolated pancreas DCs with LPS (and PBS), incubated for 18h and measured gene expression. We compared gene expression between strains NOD vs C57BL/6 under steady-state and after in-vitro LPS/PBS stimulation.
2014-07-01 | E-GEOD-45028 | biostudies-arrayexpress