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:Macroscopic mechanostress can disrupt nuclear envelop integrity of cancer cell. However, the impact of this stimuli on the tumor microenvironment remians unclear. Here, by constructing a single-cell RNA sequencing data of hindpaw-engrafted B16F10 melanoma with/without forced wheel running, we show that reorganization of fibroblast and macrophage subtypes. Fibroblasts from running group showed upregulated Acta2 and Lrrc15 expression with increased ECM production. IL-1b expressing macrophage subtype proportion was increased in running group. Collectively, these data elucidate the changes within the tumor microenvironment upon macroscopic mechanostress.
2026-06-01 | GSE289587 | GEO
Project description:Localized rupture of the nuclear envelope has been reported in various pathologies, including cancer, neurodegenerative disease, myocardial infarction, as well as dilated cardiomyopathy caused by Lamin A/C gene mutations (LMNA-DCM). Whether and how nuclear rupture contributes to disease remains unclear. Here, we report that nuclear rupture causes global transcriptional deficiency in a mouse model of LMNA-DCM. We observed that ruptured nuclei lost chromatin-bound RNA polymerase II, leading to downregulation of numerous genes essential for cardiomyocyte structure and function. Notably, over one third of ruptured nuclei resealed and regained transcription. Resealing involved the ESCRT-III membrane remodeling complex and was cardioprotective, as its blockade increased rupture frequency and accelerated cardiomyopathy. However, resealing was ineffective: resealed nuclei re-ruptured at twice the resealing rate and ten-fold faster than the de novo rupture rate. A mathematical model predicted a steady accumulation of ruptured nuclei despite ongoing resealing. Consistently, a human LMNA-mutant heart contained numerous ruptured nuclei at the time of disease presentation. These findings link nuclear rupture to organ deterioration through global transcriptional deficiency and suggested rupture repair as a critical modifier of nuclear rupture-associated conditions.
2026-04-03 | GSE325163 | GEO
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:Nuclear envelope rupture causes RNA polymerase loss in LMNA cardiomyopathy
| PRJNA1438739 | ENA
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