Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cell confinement memory initiates heritable loss of chromosomes and a persistently dysregulated division program

ABSTRACT: Heritable genetic changes continually arise in cancer, especially in solid tumors where cells sometimes appear compressed. Rare heritable losses of chromosomes in live cells are quantified here with chromosome reporters (ChReporters) that show similar losses after mild or strong compression. Mild compression (to <40% of interphase height) perturbs mitotic spindles and prolongs pro/metaphase but ruptures few nuclei compared to strong compression. Unexpectedly, chromosome mis-segregation into micronuclei emerges only after release from mild confinement, but arrest and death predominate. All such effects are phenocopied by Nocodazole washout that induces a ‘memory’ of prolonged mitosis. The results differ from transient inhibition of the spindle assembly checkpoint and cell cycle entry with a CDK4/6-inhibitor – both of which quickly generate micronuclei. Single-cell-RNA-sequencing confirms chromosome loss days after confinement and reveals persistent upregulation of chromosome segregation. The results suggest a mitotic memory of confinement, addressing a significant gap in mechanobiology and cancer evolution.

ORGANISM(S): Homo sapiens

PROVIDER: GSE317816 | GEO | 2026/01/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE317816_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 3 of 3

Similar Datasets

Gene expression analysis of MTBTOM tumors

Project description:Tumors that overexpress the MYC oncogene frequently demonstrate aneuploidy, numerical chromosome alterations associated with highly aggressive cancers, rapid tumor evolution, and poor patient outcome. Here, we identify that MYC overexpression induces defects in microtubule nucleation and mitotic spindle assembly, promoting chromosome segregation defects, micronuclei and chromosomal instability (CIN). High TPX2 expression is permissive for mitotic spindle assembly and chromosome segregation in cells with MYC overexpression; whereas TPX2 depletion blocks mitotic progression, induces cell death and prevents tumor growth. Attenuating MYC expression reverses mitotic defects, even in established tumor cell lines, implicating an ongoing role for high MYC in the persistence of CIN in tumors. Our studies implicate the MYC oncogene as a regulator of spindle assembly and identify a new MYC-TPX2 synthetic-lethal interaction that could represent a future therapeutic strategy in MYC-overexpressing cancers. Moreover, our studies suggest that blocking MYC activity can attenuate the emergence of CIN and tumor evolution.

2020-03-30 | GSE130921 | GEO

Gene expression analysis of EuMyc lymphoma cells after MYC inactivation

2020-03-30 | GSE130920 | GEO

Cohesin removal reprograms mitotic gene expression upon mitotic entry [RNA-seq I]

Project description:During mitosis, the genome is restructured to facilitate chromosome segregation, accompanied by dramatic changes in gene expression. However, the mechanisms that underlie mitotic transcriptional regulation are unclear. In contrast to transcribed genes, centromere regions retain transcriptionally active RNA Polymerase II (RNAPII) in mitosis. Here, we demonstrate that chromosome-localized cohesin is necessary and sufficient to retain active RNAPII on mitotic centromeres. Failure to remove cohesin from mitotic chromosome arms dramatically alters mitotic gene expression, and results in a failure to release elongating RNAPII and nascent transcripts from mitotic chromosomes. We propose that prophase cohesin removal is the key step in reprogramming gene expression as cells transition from G2 to mitosis, and is temporally coupled with chromosome condensation to coordinate chromosome segregation with changes in gene expression.

2020-01-30 | GSE130558 | GEO

Cohesin removal reprograms mitotic gene expression upon mitotic entry [ChIP-seq]

2020-01-30 | GSE139846 | GEO

Cohesin removal reprograms mitotic gene expression upon mitotic entry [RNA-seq II]

2020-01-30 | GSE139845 | GEO

Retinoic acid-induced 2 protein contributes to proficient homologous recombination and maintains genomic stability in breast cancer

Project description:Genome instability is a fundamental feature and hallmark of cancer associated with aggressiveness, drug resistance and poor prognosis. Here, we provide evidence for an essential function of the Retinoic acid-induced 2 (RAI2) protein as a suppressor of genome instability. Analysis of clinical samples revealed that in primary breast tumors, low RAI2 gene expression is significantly associated with genomically unstable tumors and poor prognosis. RAI2 depletion in breast cancer cell lines resulted in loss of mitotic fidelity characterized by prolonged mitosis with increased chromosome segregation errors and micronuclei formation. Drug screening revealed increased sensitivity of RAI2-depleted breast cancer cells to topoisomerase I and Aurora A inhibitors. We also found that genotoxic stress induces RAI2 protein, which shows affinity for poly-(ADP-ribose) and contributes to efficient DNA repair by homologous recombination. We validated the functional association of RAI2 gene expression with DNA double-strand break repair capacity in clinical samples. Our findings support, for the first time, an important functional role of RAI2 in the maintenance of mitotic fidelity and DNA repair associated with early metastatic relapse.

2025-08-04 | PXD047189 | Pride

Effect of chronic mechanical compression on immortalized human astrocytes

Project description:Immortalized human astrocytes were subjected to a controlled in vitro model of chronic mechanical compression to investigate how solid stress—similar to that exerted by growing brain tumors—directly affects astrocyte transcriptional programs. RNA sequencing was performed after 24 hours of compression to measure sustained mechanotransductive responses. Compressed astrocytes showed robust induction of AP-1-associated immediate-early genes and activation of NF-κB–dependent inflammatory pathways. These data define the transcriptional signatures by which human astrocytes detect and respond to mechanical stress, providing a resource for understanding mechanobiology and neuroinflammatory signaling in diseases featuring mass effect, including glioblastoma and traumatic brain injury.

2025-12-18 | GSE313613 | GEO

Chromosomal instability promotes metastasis through a cytosolic DNA response

Project description:Chromosomal instability (CIN) is a hallmark of cancer, and it results from ongoing errors in chromosome segregation during mitosis. While CIN is a major driver of tumor evolution, its role in metastasis has not been established. Here we show that CIN promotes metastasis by sustaining a tumor-cell autonomous inflammatory response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose envelopes frequently rupture exposing their DNA content to the cytosol. This leads to the activation of the cGAS-STING cytosolic DNA-sensing pathway and downstream noncanonical NF-kB signaling. Genetic suppression of CIN significantly delays metastasis in transplantable tumor models, whereas inducing chromosome segregation errors promotes cellular invasion and metastasis in a STING-dependent manner. In contrast to primary tumors, human and mouse metastases strongly select for CIN, in part, due to its ability to enrich for metastasis-initiating mesenchymal subpopulations, offering an opportunity to target chromosome segregation errors for therapeutic benefit.

2018-01-15 | GSE98183 | GEO

Real-time dynamics of Plasmodium Ndc80 reveals unusual modes of chromosome segregation during parasite proliferative stages

Project description:Eukaryotic cell proliferation requires chromosome replication and precise segregation to ensure daughter cells have identical genomic copies. The genus Plasmodium, the causative agent of malaria, has developed remarkable characteristic of nuclear division throughout its lifecycle to meet some peculiar and unique challenges of DNA replication and chromosome segregation. The parasite undergoes atypical endomitosis and endoreduplication with an intact nuclear membrane and intranuclear mitotic spindle. To understand diverse modes of cell division in Plasmodium we have studied the behaviour and composition of a key part of the mitotic apparatus, the outer kinetochore Ndc80 complex that attaches the centromere of chromosomes to the microtubules of the mitotic spindle. Using Ndc80 live-cell imaging in Plasmodium berghei we observe dynamic changes throughout proliferative life-stages including highly unusual kinetochore arrangements in sexual stages of the parasite. Furthermore, we identify a divergent Spc24 component of Ndc80 complex, previously thought to be missing, and completing a canonical, albeit unusual, Ndc80 complex structure. Altogether our studies reveal the kinetochore as an ideal starting point towards understanding non-canonical modes of chromosome segregation and cell division in Plasmodium.

2020-06-09 | PXD017619 | Pride

Quantification of histone H3 and H4 modifications by mass spectrometry in wildtype and MCM2-2A mutants of mice ESCs

Project description:During DNA replication modified parental histones H3-H4 are segregated almost symmetrically to the two daughter DNA strands enabling mitotic inheritance of histone PTMs. Whether heritable histone modifications confer epigenetic regulation by maintaining chromatin states and gene expression is unclear. Using MCM2 histone-binding mutant embryonic stem cells (ESCs) and mass spectrometry, we show that asymmetric segregation of parental histones to the leading strand causes imbalanced inheritance of histone H3K27 methylations to daughter cells.

2023-08-30 | PXD020326 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data