Deciphering the molecular alterations sustaining an inverted apicobasal polarity phenotype in colorectal cancer clusters (Tumour Spheres with Inverted Polarity, TSIPs)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA638924 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Colorectal cancer (CRC) is the second deadliest form of cancer and most of patients die from their metastases. As previously shown by our team, in serrated CRC patients, metastases are due to spherical clusters of epithelial cancer cells displaying an inverted apicobasal polarity. We called them TSIPs for Tumor spheres with inverted polarity. In this study, we investigated the alterations sustaining this remarkable phenotype using PDXs and organoids techniques. In particular, we compared a model that respond normally to its microenvironment (mainly 3D collagen-I networks) to two models that keep their inverted polarity. A whole transcriptome investigation allowed us to better understand the mechanisms of such a topology.
2021-01-31 | GSE152299 | GEO
Project description:DNA replication errors are a major driver of evolutionâ??from single nucleotide polymorphisms to large-scale copy number variations (CNVs). Here we test a specific replication-based model to explain the generation of interstitial, inverted triplications. While no genetic information is lost, the novel inversion junctions and increased copy number of the included sequences create the potential for adaptive phenotypes. The modelâ??Origin-Dependent Inverted-Repeat Amplification (ODIRA)â??proposes that a replication error at pre-existing short, interrupted, inverted repeats in genomic sequences generates an extrachromosomal, inverted dimeric, autonomously replicating intermediate; subsequent genomic integration of the dimer yields this class of CNV without loss of distal chromosomal sequences. We used a combination of in vitro and in vivo approaches to test the feasibility of the proposed replication error and its downstream consequences on chromosome structure in the yeast Saccharomyces cerevisiae. We show that the proposed replication errorâ??the ligation of leading and lagging nascent strands to create a "closed" forkâ??can occur in vitro at short, interrupted inverted repeats. The removal of molecules with closed forks results in a hairpin-capped linear duplex that we show replicates in vivo to create an inverted, dimeric plasmid that subsequently integrates into the genome by homologous recombination, creating an inverted triplication. While other models have been proposed to explain inverted triplications and their derivatives, our model can also explain the generation of human, de novo, inverted amplicons that have a 2:1 mixture of sequences from both homologues of a single parentâ??a feature readily explained by a plasmid intermediate that arises from one homologue and integrates into the other homolog prior to meiosis. Our tests of key features of ODIRA lend support to this mechanism and suggest further avenues of enquiry to unravel the origins of interstitial, inverted CNVs pivotal in human health and evolution These are all CGH arrays comparing DNA copy number between evolved yeast strains and a euploid wt strain.
2015-10-30 | E-GEOD-74443 | biostudies-arrayexpress
Project description:Inverted duplications are a common type of copy number variation (CNV) in germline and somatic genomes. Large duplications that include many genes can lead to both neurodevelopmental phenotypes in children and gene amplifications in tumors. There are several models for inverted duplication formation, most of which include a dicentric chromosome intermediate followed by breakage-fusion-bridge (BFB) cycles, but the mechanisms that give rise to the inverted dicentric chromosome in most inverted duplications remain unknown. Here we have combined high-resolution array CGH, custom sequence capture, next-generation sequencing, and long-range PCR to analyze the breakpoints of 50 nonrecurrent inverted duplications in patients with intellectual disability, autism, and congenital anomalies. Sequence analysis of breakpoint junctions reveals a normal-copy disomic spacer between inverted and non-inverted copies of the duplication. Further, short inverted repeats are present at the boundary of the disomic spacer and the inverted duplication. These data support a mechanism of inverted duplication formation whereby a chromosome with a double-strand break intrastrand pairs with itself to form a “hairpin” intermediate that, after DNA replication, produces a dicentric inverted chromosome with a disomic spacer corresponding to the site of the hairpin. We also find evidence of short insertions and inversions at inverted duplication junctions, consistent with a DNA replication-based CNV mechanism. This process can give rise to inverted duplications adjacent to terminal deletions, inverted duplications juxtaposed to translocations, and inverted duplication ring chromosomes High resolution array CGH; two-color experiment, clinical patient vs. normal control gDNA; sex mis-matched
2013-04-03 | E-GEOD-45395 | biostudies-arrayexpress
Project description:DNA replication errors are a major driver of evolution—from single nucleotide polymorphisms to large-scale copy number variations (CNVs). Here we test a specific replication-based model to explain the generation of interstitial, inverted triplications. While no genetic information is lost, the novel inversion junctions and increased copy number of the included sequences create the potential for adaptive phenotypes. The model—Origin-Dependent Inverted-Repeat Amplification (ODIRA)—proposes that a replication error at pre-existing short, interrupted, inverted repeats in genomic sequences generates an extrachromosomal, inverted dimeric, autonomously replicating intermediate; subsequent genomic integration of the dimer yields this class of CNV without loss of distal chromosomal sequences. We used a combination of in vitro and in vivo approaches to test the feasibility of the proposed replication error and its downstream consequences on chromosome structure in the yeast Saccharomyces cerevisiae. We show that the proposed replication error—the ligation of leading and lagging nascent strands to create “closed” forks—can occur in vitro at short, interrupted inverted repeats. The removal of molecules with two closed forks results in a hairpin-capped linear duplex that we show replicates in vivo to create an inverted, dimeric plasmid that subsequently integrates into the genome by homologous recombination, creating an inverted triplication. While other models have been proposed to explain inverted triplications and their derivatives, our model can also explain the generation of human, de novo, inverted amplicons that have a 2:1 mixture of sequences from both homologues of a single parent—a feature readily explained by a plasmid intermediate that arises from one homologue and integrates into the other homologue prior to meiosis. Our tests of key features of ODIRA lend support to this mechanism and suggest further avenues of enquiry to unravel the origins of interstitial, inverted CNVs pivotal in human health and evolution.
2015-10-30 | GSE74443 | GEO
Project description:Inverted duplications are a common type of copy number variation (CNV) in germline and somatic genomes. Large duplications that include many genes can lead to both neurodevelopmental phenotypes in children and gene amplifications in tumors. There are several models for inverted duplication formation, most of which include a dicentric chromosome intermediate followed by breakage-fusion-bridge (BFB) cycles, but the mechanisms that give rise to the inverted dicentric chromosome in most inverted duplications remain unknown. Here we have combined high-resolution array CGH, custom sequence capture, next-generation sequencing, and long-range PCR to analyze the breakpoints of 50 nonrecurrent inverted duplications in patients with intellectual disability, autism, and congenital anomalies. Sequence analysis of breakpoint junctions reveals a normal-copy disomic spacer between inverted and non-inverted copies of the duplication. Further, short inverted repeats are present at the boundary of the disomic spacer and the inverted duplication. These data support a mechanism of inverted duplication formation whereby a chromosome with a double-strand break intrastrand pairs with itself to form a “hairpin” intermediate that, after DNA replication, produces a dicentric inverted chromosome with a disomic spacer corresponding to the site of the hairpin. We also find evidence of short insertions and inversions at inverted duplication junctions, consistent with a DNA replication-based CNV mechanism. This process can give rise to inverted duplications adjacent to terminal deletions, inverted duplications juxtaposed to translocations, and inverted duplication ring chromosomes
2013-04-03 | GSE45395 | GEO
Project description:In this study, we performed miRNA profiles analysis of 84, 17, 20, 83, 718, 1123, 528 and 816 glioma spheres compared to normal progenitor sample (16wf) using microarray to evaluate their potential role in regulation of the biological properties of proneural and mesenchymal glioma spheres
2016-07-07 | GSE84106 | GEO
Project description:Rhabomyosarcoma cells can be cultured in stem cell medium over several passages and form spheres being enriched in putative cancer stem cell markers and expressing high levels of stem cell genes. In this dataset, we include RNA samples from 2 rhabdomyosarcoma cell lines and 3 different sphere passages of each cell line. 16 samples were analyzed and all sphere passages were compared to the expression level of their corresponding adherent cell line. We wanted to see an up- or downregulation of genes in the spheres to identify new potential cancer stem cell marker.
2011-04-30 | E-GEOD-26635 | biostudies-arrayexpress
Project description:The mammalian cell nucleus displays a remarkable spatial segregation of active euchromatic from inactive heterochromatic genomic regions. In conventional nuclei, euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery. In contrast, rod photoreceptors in nocturnal mammals have inverted nuclei, with a dense heterochromatic core and a thin euchromatic outer shell. This inverted architecture likely converts rod nuclei into microlenses to facilitate nocturnal vision, and may relate to the absence of particular proteins that tether heterochromatin to the lamina. However, both the mechanism of inversion and the role of interactions between different types of chromatin and the lamina in nuclear organization remain unknown. To elucidate this mechanism we performed Hi-C and microscopy on cells with inverted nuclei and their conventional counterparts. Strikingly, despite the inversion evident in microscopy, both types of nuclei display similar Hi-C maps. To resolve this paradox we developed a polymer model of chromosomes and found a universal mechanism that reconciles Hi-C and microscopy for both inverted and conventional nuclei. Based solely on attraction between heterochromatic regions, this mechanism is sufficient to drive phase separation of euchromatin and heterochromatin and faithfully reproduces the 3D organization of inverted nuclei. When interactions between heterochromatin and the lamina are added, the same model recreates the conventional nuclear organization. To further test our models, we eliminated lamina interactions in models of conventional nuclei and found that this triggers a spontaneous process of inversion that qualitatively reproduces the pathway of morphological changes during nuclear inversion in vivo. Together, our experiments and modeling suggest that interactions among heterochromatic regions are central to phase separation of the active and inactive genome in inverted and conventional nuclei, while interactions with the lamina are essential for building the conventional architecture from these segregated phases. Ultimately our data suggest that an inverted organization constitutes the default state of nuclear architecture.
2019-02-22 | GSE111032 | GEO
Project description:Sinonasal papilloma is the most common type of sinonasal tumor, with the inverted variant being the most frequent subtype. This variant is known for its potential for recurrence and propensity for malignant transformation. The aim of this study is to investigate the biomarkers and regulatory pathways involved in the development of sinonasal inverted papilloma (SNIP).
2024-12-27 | GSE270193 | GEO
Project description:In this study, we performed miRNA profiles analysis of 84, 17, 20, 83, 718, 1123, 528 and 816 glioma spheres compared to normal progenitor sample (16wf) using microarray to evaluate their potential role in regulation of the biological properties of proneural and mesenchymal glioma spheres miRNA profiling analysis of the 9 samples including 8 patient-derived samples including glioma sphere samples (84, 17, 20, 718, 816, 528, 83 and 1123), as well as one normal progenitor sample (16wf).
2016-07-07 | E-GEOD-84106 | biostudies-arrayexpress