SUN1/2 Controls Macrophage Polarization via Modulating Nuclear Size and Stiffness
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1019379 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26128864_1.fastq.gz | Fastqsanger.gz | |||
| SRR26128864_2.fastq.gz | Fastqsanger.gz | |||
| SRR26128865_1.fastq.gz | Fastqsanger.gz | |||
| SRR26128865_2.fastq.gz | Fastqsanger.gz | |||
| SRR26128866_1.fastq.gz | Fastqsanger.gz |
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Project description:Alteration of the size and stiffness of the nucleus triggered by environmental cues are thought to be important for eukaryotic cell fate and function. Here we identify the nuclear envelope proteins SUN1/2 as mechano-regulators of the nucleus during M1 polarization of the macrophage. Specifically, we show that LPS treatment decreases the protein levels of SUN1/2 in a CK2-bTrCP-dependent manner to shrink and soften the nucleus, therefore altering the chromatin accessibility for M1-associated gene expression.
2023-09-28 | GSE243684 | GEO
Project description:Alteration of the size and stiffness of the nucleus triggered by environmental cues are thought to be important for eukaryotic cell fate and function. However, it remains unclear how context-dependent nuclear remodeling occurs and reprograms gene expression. Here we identify the nuclear envelope proteins SUN1/2 as mechano-regulators of the nucleus during M1 polarization of the macrophage. Specifically, we show that LPS treatment decreases the protein levels of SUN1/2 in a CK2-βTrCP-dependent manner to shrink and soften the nucleus, therefore altering the chromatin accessibility for M1-associated gene expression. Notably, the transmembrane helix of SUN1/2 is solely required and sufficient for the nuclear mechano-remodeling. Consistently, SUN1/2 depletion in macrophages facilitates their phagocytosis, tissue infiltration, and proinflammatory cytokine production, thereby boosting the antitumor immunity in mice. Thus, our study demonstrates that, in response to inflammatory cues, SUN1/2 proteins act as mechano-regulators to remodel the nucleus and chromatin for M1 polarization of the macrophage.
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Project description:The substrate stiffness plays an important role in mediating the cellular behavior. Neutrophils predominate the early inflammatory response and initiate the regeneration. The neutrophil activation can be regulated by physical cues. However, it is not known how neutrophils respond to substrate stiffness, which is of significant importance in determining the outcomes of engineered tissue mimics. Herein, a three-dimensional culture system made of hydrogel for bone marrow-derived neutrophils was developed to explore the effects of varying stiffness (1.5, 2.6, and 5.7 kPa) on neutrophil phenotype and polarization states.
2022-12-03 | GSE217379 | GEO
Project description:The inner nuclear envelope (NE) proteins interact with the nuclear lamina and participate in the architectural compartmentalization of chromosomes. The association of NE proteins with DNA contributes to the spatial rearrangement of chromosomes and their gene expression. Sun1 is an inner nuclear membrane (INM) protein that locates to telomeres and anchors chromosome movement in the prophase of meiosis. Here, we have created Sun1-/- mice and found that these mice are born and grow normally but are reproductively infertile. Detailed molecular analyses showed that Sun1-/- P14 testes are repressed for the expression of reproductive genes and have no detectable piRNA. These findings raise a heretofore unrecognized role of Sun1 in the selective gene expression of coding and non-coding RNAs needed for gemetogenesis. Total RNA was isolated from E14.5 mouse embryonic fibroblasts (MEFs) and and day 9 and 14 mouse whole testes. cDNA samples from paired (same parents) wt (Cy3-labled) and Sun1-/- (Cy5-labled) mice were mixed and hybridized.
2009-03-11 | E-GEOD-12867 | biostudies-arrayexpress
Project description:SUN1 was identified in a screen for fertility genes in Plasmodium berghei. To understand its role, SUN1 was tagged with an HA tag at the endogenous locus, and SUN1 interacting proteins were characterised by affinity purification followed by mass spectrometry. This led to the identification of allantoicase as a SUN1-associated protein. Subsequent affinity interaction proteomics of HA-tagged allantoicase confirmed the interaction between these two proteins.
2024-10-24 | PXD048341 | Pride
Project description:T cell infiltration is essential for immune checkpoint inhibitors to be effective in treating solid cancers. Through a bioinformatic pipeline, we identified a target gene SUN1 that might relate to modulating immune cell infiltration and immune response. Thus, we generated one Sun1_knockout CT26 cell line (Sun1_KO) and two control CT26 cell lines (Sun1_Control) using CRISPR-Cas9. By performing RNA-seq on cultured cells, tumors grown in syngeneic model, and purified tumor cells from tumors grown in syngeneic model, we set out to understand how mouse Sun1 can affect immune-related pathways and immune cell infiltration and anti-PD1 efficacy in BALB/c mice.
2024-03-29 | GSE250602 | GEO
Project description:T cell infiltration is essential for immune checkpoint inhibitors to be effective in treating solid cancers. Through a bioinformatic pipeline, we identified a target gene SUN1 that might relate to modulating immune cell infiltration and immune response. Thus, we generated one Sun1_knockout CT26 cell line (Sun1_KO) using CRISPR-Cas9. By performing multiome single nuclei sequencing using tumors grown in syngeneic model, we set out to understand how mouse Sun1 can affect the regulatory network in tumor cells in vivo.
2024-03-29 | GSE262237 | GEO
Project description:Mesenchyal Stem Cells (MSCs) differentiation into multiple lineages, such as osteocytes and adipocytes, has been shown to be regulated by mechanical signals. The Linker of the Nucleoskeleton and Cytoskeleton (LINC) complex has been shown to be required for mechanical signal transduction, regulation of MSCs differentiation, and nuclear integrity. The LINC complex is made of Nesprins and Sun proteins. Nesprin proteins associate with the cytoskeleton on the outer nuclear membrane and Sun proteins are bound to the inner nuclear membrane where they bind to inner nuclear proteins and chromatin. We investigated the role of the Sun1/2 in regulating the inner nuclear functions of chromatin organization and adipogenic differentiation independently of the LINC complex function. We show that depletion of Sun1/2 increased nuclear area and perimeter, and decreased circularity. Expression of a dominant-negative KASH (dnKASH) domain targeting the SUN domain on Sun proteins inhibiting Nesprin-SUN association resulting a loss of Nesprin localization to the nuclear envelope decreased nuclear area and circularity. Adipogenesis was inhibited during Sun1/2 depletion while dnKASH expression accelerated adipgoenesis. RNA-seq data showed decreased adipogensis and increased immune response during Sun1/2 depletion. dnKASH responded oppositely with increased adipogenic gene expression and decreased immune response. We also observed increased H3K9me3 levels, increased H3K9me3 foci count, and enrichment on Adipoq during Sun1/2 depletion. No increase of H3K9me3 levels, foci count, or increased H3K9me3 enrichment on Adipoq was found during dnKASH expression. We conclude that physically decoupling of the LINC complex via dnKASH accelerates adipogenesis and that Sun1/2 regulates chromatin organization and adipogenesis independently of the LINC complex function.
2022-07-13 | GSE193505 | GEO
Project description:Aim: To investigate the effect and mechanism of Sitagliptin phosphate on inflammation and macrophage polarization in a mouse model of type 2 diabetes. Methods: In vitro, Raw264.7 cells were cultured with a high concentration of glucose (HG) and sitagliptin phosphate (SIG). The levels of inflammatory factors and the regulation of macrophage polarization were investigated, and the differentially expressed genes between HG and HG+SIG intervention were analyzed and enriched through transcriptomics. In vivo, C57BL/6J male mice were treated with HFD+STZ to establish a type 2 diabetes mouse model were investigated the effects of regulation of macrophage polarization in the pancreas and visceral adipose tissue. Results:In vitro cell experiments and transcriptomics showed that Sitagliptin phosphate decreased the secretion of inflammatory factors IL-6 and TNF-α induced by high-glucose, and increased secretion of anti-inflammatory factor IL-10 by enhancing macrophage polarization. In vivo, the body weight and abdominal visceral fat weight, the ratio of visceral fat weight to body weight and fasting blood glucose were significantly increased in the DM group compared with the Control (P<0.05), Sitagliptin phosphate treatments reversed the changes in the DM group. Moreover, histological analysis showed that compared with the Control group, the size of visceral adipocytes, hepatocyte lipid deposition and the ratio of M1/M2 macrophage were higher in the DM group, which were reversed by Sitagliptin phosphate treatments (P<0.05), insulin treatments did not have a significant effect(P＞0.05).Mechanistically, Western blot showed that compared with the normal group, HG upregulated the expression of mTORc1 protein, P-65 phosphorylation and P-65 protein expression in Raw264.7 cells (P<0.05), downregulated the expression of IKKβ (P<0.05) and PPAR-γ proteins (P<0.05), Sitagliptin phosphate and insulin treatments rescued these changes. Conclusion: These results indicated that Sitagliptin phosphate reduced high glucose-induced inflammation by improving the imbalance of macrophage polarization via modulating the mTORc1/ PPAR-γ/NF-κB in vitro and in vivo.
2025-04-03 | GSE293313 | GEO
Project description:The inner nuclear envelope (NE) proteins interact with the nuclear lamina and participate in the architectural compartmentalization of chromosomes. The association of NE proteins with DNA contributes to the spatial rearrangement of chromosomes and their gene expression. Sun1 is an inner nuclear membrane (INM) protein that locates to telomeres and anchors chromosome movement in the prophase of meiosis. Here, we have created Sun1-/- mice and found that these mice are born and grow normally but are reproductively infertile. Detailed molecular analyses showed that Sun1-/- P14 testes are repressed for the expression of reproductive genes and have no detectable piRNA. These findings raise a heretofore unrecognized role of Sun1 in the selective gene expression of coding and non-coding RNAs needed for gemetogenesis.
2009-03-11 | GSE12867 | GEO