Effects of NIK activation on the self-renewal of hematopoietic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE88949 | GEO | 2017/10/19
SECONDARY ACCESSION(S): PRJNA349172
REPOSITORIES: GEO
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Project description:Arabidopsis was transformed with the NIK receptor or the mutant T474D NIK receptor and infected with CaLCuV. The global variation of gene expression was analysed by RNA-seq at 10 days post inoculation and 20 days post inoculation and differential gene expression was determinated in comparison with mock inoculated Arabidopsis lines. Pairwise comparison between mock inoculated and infected genotypes (WT,NIK-expressing lines and T474D-expressing lines) at 10 dpi and 20 dpi
2014-04-21 | E-GEOD-56922 | biostudies-arrayexpress
Project description:The genetic programs that maintain hematopoiesis during steady state in physiologic conditions are different from those activated during stress. Here we show that hematopoietic stem cells (HSCs) with deficiencies in components of the alternative NFkB pathway (the NFkB inducing kinase, NIK, and the downstream molecule NFkB2) had a defect in response to stressors such as supraphysiological doses of cytokines, chemotherapy and hematopoietic transplantation. NIK-deficient mice had peripheral blood and bone marrow leukocyte numbers within normal ranges (except for the already reported defects in B-cell maturation), however, HSCs showed significantly slower expansion capacity in in vitro cultures compared to wild type HSCs. This was due to a delayed cell cycle and increased apoptosis. In vivo experiments showed that NIK-deficient HSCs did not recover at the same pace as controls when challenged with myeloablative chemotherapy. Finally, NIK-deficient HSCs showed a significantly decreased competitive repopulation capacity in vivo. Using HSCs from mice deficient in one of two downstream targets of NIK, i.e., either NFkB2 or c-Rel, only NFkB2 deficiency recapitulated the defects detected with NIK-deficient HSCs. Our results underscore the role of NIK and the alternative NFkB pathway for the recovery of normal levels of hematopoiesis after stress.
2014-11-29 | GSE63702 | GEO
Project description:Previously we have shown that loss of non-canonical NF-?B signaling impairs self-renewal of hematopoietic stem/progenitor cells (HSPCs). This prompted us to investigate whether persistent activation of the non-canonical NF-?B signaling will have supportive effects on HSPC self-renewal. NF-?B-inducing kinase (NIK) is an important kinase that mainly activates the non-canonical pathway through directly phosphorylating IKK?. In contrast to our expectations, constitutive activation of NIK in the hematopoietic system leads to bone marrow (BM) failure and postnatal lethality due to intrinsic impairment of HSPC self-renewal and extrinsic disruption of BM microenvironment through enhancing osteoclastogenesis. The impaired HSPC function is associated with reduced cell proliferation and increased apoptosis and inflammatory cytokine responses. RNAseq analysis of control and NIK-activated HSPCs reveals that these effects are through non-canonical NF-?B signaling without significant changes in the canonical pathway. Gene set expression analysis of RNAseq data reveals globally decreased stem cell signature, increased maturation signature, and increased inflammatory responses. Many genes (Mpl, Tifab, Emcn, Flt3, Bcl2, and others) that regulate HSPC self-renewal, lineage commitment, and apoptosis are significantly downregulated-and those genes that regulate inflammatory responses and cell cycle inhibition (Cdkn2a and Cdkn2b) are significantly upregulated-by activation of NIK. Importantly, our data demonstrate that activation of NIK-non-canonical signaling has distinct phenotypes-smaller spleen size, decreased white blood cell counts, and reduced HSPC proliferation-compared to activation of canonical signaling. Collectively, these data indicate that the balanced non-canonical NF-?B signaling is essential for maintaining normal hematopoiesis and NIK-non-canonical signaling contributes to the development of BM failure. Stem Cells 2017;35:777-786.
| S-EPMC5817891 | biostudies-other
Project description:Arabidopsis was transformed with the NIK receptor or the mutant T474D NIK receptor and infected with CaLCuV. The global variation of gene expression was analysed by RNA-seq at 10 days post inoculation and 20 days post inoculation and differential gene expression was determinated in comparison with mock inoculated Arabidopsis lines.
2014-04-21 | GSE56922 | GEO
Project description:Our findings establish NIK as a pivotal regulator of T cell metabolism in anti-tumor immunity and highlight a posttranslational mechanism of metabolic regulation involving the G6PD-NADPH redox system. CoIP assays revealed a strong physical interaction between NIK and G6PD in both T cells and transiently transfected 293 cells, suggesting G6PD to be a direct target of NIK. Using a phosphoprotein gel analysis approach, we demonstrated that NIK expression stimulated G6PD phosphorylation. To further study the mechanism, we performed mass spectrometry identify phosphorylation sites of G6PD stimulated by NIK
2020-10-05 | PXD020943 | Pride
Project description:Purpose: The goal of this study is to determine the molecular mechanisms involved in the NIK regulation of α cell function. Methods: mRNA profiles of β-Gal control, NIK, and NIK(KA) overexpressed αTC1-6 cells were generated by deep sequencing using an Illumina Hiseq platform. Paired-end clean reads were aligned to the mouse reference genome(Ensemble_GRCm38.89) with TopHat (version 2.0.12), and the aligned reads were used to quantify mRNA expression by using HTSeq-count (version 0.6.1). Conclusion: Our study represents the first detailed analysis of NIK-overexpressing aTC1-6 cell transcriptomes, generated by RNA-seq technology. Our results show that 328 genes were upregulated and 48 genes were downregulated following NIK overexpression. GO analysis indicated that the upregulated genes were primarily related to the immune response. KEGG pathway enrichment analysis showed that immune signaling pathways, including the TNF, NF-κB, and chemokine signaling pathways, were significantly activated by NIK overexpression in aTC1-6 cells, while genes related to metabolism-associated signal pathways were significantly decreased. NIK(KA), the dominant-negative mutant of NIK, does not affect gene expression in aTC1-6 cells.
2018-12-30 | GSE112511 | GEO
Project description:Comparison of transcriptome between control and NIK-stabilized leukemia stem cells
2018-01-03 | GSE97389 | GEO
Project description:To generate an efficient defense against begomovirus, we modulated the activity of the immune defense receptor NIK (NSP-Interacting Kinase) in tomato plants; NIK is a virulence target of the begomovirus NSP during infection. Replacing threonine-474 with aspartate (T474D) within the kinase activation loop promoted the constitutive activation of NIK-mediated defenses. This activation resulted in the down-regulation of translation-related genes and the suppression of global translation in T474D-overexpressing tomato lines. We also found that T474D-induced defense-related transcripts were associated with polysomes and immune proteins, which accumulated to detectable levels in T474D leaves. Consistent with these findings, T474D transgenic lines were tolerant to the tomato-infecting begomoviruses ToYSV and ToSRV. We propose that NIK mediates an anti-viral response via translation suppression and immune system induction. Global variation on gene expression induced by NIK expression and virus infection using total RNA from mock-inoculated and ToYSV-infected tomato wild-type plants, mock-inoculated and infected 35S::NIK1-4 overexpressing lines and mock-inoculated and infected 35S::T474D overexpressing lines. File map_itag23.csv correlates the ITAG 2.3 cDNA ID with the 21 bp reads in file Profiles_with_differential_expressions.csv.
2013-12-17 | E-GEOD-38028 | biostudies-arrayexpress
Project description:Purpose: The goal of this study is to investigate how NIK regulates islet β-cell function. Methods: mRNA profiles of β-Gal-overexpressing, NIK-overexpressing, and NIK(KA)-overexpressing INS-1 832/13 cells were generated by deep sequencing using an Illumina Hiseq platform. Paired-end clean reads were aligned to the rat reference genome (ftp://ftp.ensembl.org/pub/release-90/fasta/rattus_norvegicus/dna/) with TopHat (version 2.0.12), and the aligned reads were used to quantify mRNA expression by using HTSeq-count (version 0.6.1). Conclusion: Our study represents the first detailed analysis of mRNA profiles in NIK-overexpressing and NIK(KA)-overexpressing INS-1 832/13 cells, generated by RNA-seq technology. Our results show that 471 genes were upregulated and 249 genes were downregulated following NIK overexpression. GO analysis indicated that the upregulated genes were primarily related to the immune response. KEGG pathway enrichment analysis showed that immune signaling pathways, including the TNF, NF-κB, antigen processing and presentation signaling pathways, were significantly activated by NIK overexpression in INS-1 832/13 cells, whereas genes related to insulin secretion and regulation of secretion were significantly decreased. NIK(KA), the dominant-negative mutant of NIK, does not induce the expression of genes related to immune response in INS-1 832/13 cells.
2020-07-28 | GSE130121 | GEO
Project description:Analysis of differentially expressed genes in MCF7 cancer cells transfected with an expression vector containing the ORF of NIK, a shRNA of NIK and a control shRNA. Transient transfections were performed in triplicates . We use micorarrays to elucidate the machanisms by which NIK regulates stem cells biology
2015-11-30 | GSE63382 | GEO