GEO accession GSE289587 is currently private and is scheduled to be released on Jan 01, 2026.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1223475 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The integrity of the nuclear envelope (NE) is essential to maintain the structural stability of the nucleus. Rupture of the NE has been frequently observed in cancer cells, especially in the context of mechanical challenges, such as physical confinement and migration. However, spontaneous NE rupture events have also been described, without any obvious physical challenges to the cell. The molecular mechanism(s) of these spontaneous NE rupture events remain to be explored. Here, we show that DNA damage and subsequent ATR activation can lead to NE rupture. Upon DNA damage, Lamin A/C is phosphorylated in an ATR-dependent manner, leading to changes in lamina assembly and, ultimately, NE rupture. In addition, we show that cancer cells with intrinsic DNA repair defects undergo frequent events of DNA damage-induced NE rupture, which renders them extremely sensitive to further NE perturbations. Exploiting this NE vulnerability could provide a new angle to complement traditional, DNA damage-based chemotherapy.
2023-10-09 | PXD040857 | Pride
Project description:The integrity of the nuclear envelope (NE) is essential to maintain the structural stability of the nucleus. Rupture of the NE has been frequently observed in cancer cells, especially in the context of mechanical challenges, such as physical confinement and migration. However, spontaneous NE rupture events have also been described, without any obvious physical challenges to the cell. The molecular mechanism(s) of these spontaneous NE rupture events remain to be explored. Here, we show that DNA damage and subsequent ATR activation can lead to NE rupture. Upon DNA damage, Lamin A/C is phosphorylated in an ATR-dependent manner, leading to changes in lamina assembly and, ultimately, NE rupture. In addition, we show that cancer cells with intrinsic DNA repair defects undergo frequent events of DNA damage-induced NE rupture, which renders them extremely sensitive to further NE perturbations. Exploiting this NE vulnerability could provide a new angle to complement traditional, DNA damage-based chemotherapy.
2023-10-09 | PXD043990 | Pride
Project description:Genomic repeats coordinate macroscopic gene function and expression
| PRJNA517472 | ENA
Project description:Subarachnoid hemorrhage due to rupture of intracranial aneurysm (IA) still has poor prognosis once after the onset in spite of modern technical advancement in medical care. The development of the novel therapeutic strategy based on molecular machineries regulating the rupture is thus mandatory for social health. Here, recent studies have clarified the potential role of neutrophil-mediated inflammatory responses in the process leading to rupture. Thereby, factors mediating the recruitment of neutrophils in situ could be the therapeutic targets to prevent rupture of IAs. In the present study, complement C5a receptor 1 (C5AR1) was picked up as the candidates from comprehensive gene expression profile data. The induction of C5AR1 in IA lesions exclusively in rupture-prone or ruptured lesions was then confirmed in immunohistochemistry. The ligand of C5AR1, C5a, was induced through the enzymatic digestion by tissue-type Plasminogen Activator and, intriguingly, forms the auto-amplification in C5a-C5AR1 axis to exacerbate neutrophil infiltration and resultant neutrophil-mediated inflammation in situ, which triggers rupture of IAs. In conclusion, we have, in the present study, examined potential factors mediating the infiltration of neutrophils into IA lesions and then identified C5a-C5AR1 axis. This cascade could become the therapeutic target to prevent rupture of IAs.
2025-09-08 | GSE242795 | GEO
Project description:Prolonged rupture of membranes (PROM) is thought to incur higher risk of neonatal infection, leading to expedited delivery and/or the use of empirical perinatal antibiotics. Here, we compared the transcriptional profile of neonatal cord blood between babies where rupture of membranes occurred greater than 24 hours before delivery (= PROM cases) and babies where rupture of membranes occurred less than 24 hours before delivery (= Control cases). On the basis that perinatal infection is more likely in births associated with PROM than those without, we tested the hypothesis that perinatal infection in a subset of births following PROM, exhibit immune responses evident in the neonatal cord blood transcriptome.
2018-12-20 | E-MTAB-6431 | biostudies-arrayexpress
Project description:Mutations in the immune-specific actin regulator WASp induce a proinflammatory state in myeloid cells, whose underlying causes remain poorly defined. Here, we applied microfabricated tools that mimic tissue mechanical forces to explore the role of WASp in connecting mechano-sensing to the activation of inflammatory responses in macrophages. We show that WASp-deficient macrophages carry nuclear structure alterations and undergo increased blebbing and nuclear rupture when exposed to mechanical confinement. High-resolution imaging indicates that WASp drives the formation of protective perinuclear actin structures in response to confinement. Functionally, WASp null macrophages respond to mechanical confinement by inducing a transcriptional profile consistent with the release of immunogenic DNA in the cytosol. The proinflammatory state of mechanically confined WASp-deficient macrophages depends, in part, on the cGAS-STING pathway of cytosolic DNA sensing. Together, these data uncover a WASp-dependent mechanism to restrict activation of inflammatory signalling in tissue macrophages and provide hints to target unabated inflammation in Wiskott-Aldrich Syndrome.
2025-03-26 | GSE285024 | GEO
Project description:Actin polymerization by WASp limits nuclear envelope rupture and inflammation in macrophages
| PRJNA1201051 | ENA
Project description:Mutations in the immune-specific actin regulator WASp induce a proinflammatory state in myeloid cells, whose underlying causes remain poorly defined. Here, we applied microfabricated tools that mimic tissue mechanical forces to explore the role of WASp in connecting mechano-sensing to the activation of inflammatory responses in macrophages. We show that WASp-deficient macrophages carry nuclear structure alterations and undergo increased blebbing and nuclear rupture when exposed to mechanical confinement. High-resolution imaging indicates that WASp drives the formation of protective perinuclear actin structures in response to confinement. Functionally, WASp null macrophages respond to mechanical confinement by inducing a transcriptional profile consistent with the release of immunogenic DNA in the cytosol. The proinflammatory state of mechanically confined WASp-deficient macrophages depends, in part, on the cGAS-STING pathway of cytosolic DNA sensing. Together, these data uncover a WASp-dependent mechanism to restrict activation of inflammatory signalling in tissue macrophages and provide hints to target unabated inflammation in Wiskott-Aldrich Syndrome.
2024-12-25 | GSE285174 | GEO
Project description:Expression analysis of migrating and non-migrating mesenchymal stromal cells (MSC) in fetal bone marrow Keywords: fetal bone marrow, mesenchymal stromal cells, migration, gene expression, genomics Three biological replates for both migrating and non-migrating mesenchymal stromal cells (MSC) in fetal bone marrow
2011-10-23 | E-GEOD-24892 | biostudies-arrayexpress
Project description:Actin polymerization by WASp limits nuclear envelope rupture and inflammation in macrophages I
| PRJNA1201748 | ENA