Targeted mutagenesis recapitulates brain tumor initiation in cerebral organoids (RNA-seq data set: 45d)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE101577 | GEO | 2018/05/30
REPOSITORIES: GEO
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Project description:Introduction of brain tumor-relevant genetic aberrations initiates different subtypes of brain tumor-like neoplasms in cerebral organoids
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Project description:Targeted mutagenesis recapitulates brain tumor initiation in cerebral organoids
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Project description:Targeted mutagenesis recapitulates brain tumor initiation in cerebral organoids (RNA-seq data set: 130d)
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Traumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent. Keywords: Traumatic brain injury, genomic response
2005-10-01 | GSE3396 | GEO
Project description:The sequential accumulation of survival advantage traits – the cancer evolution hypothesis – implies that early detection and treatment of precancers can prevent cancer mortality. In practice, detection and treatment of breast precancer ductal carcinoma in situ (DCIS) has had minimal impact on reducing breast cancer mortality. The evolution of precancer is not inevitable, suggesting that inciting neoplastic events lead to different trajectories of progression. Here we visualize distinct tumor driver gene programs of lineage specification occurring at cancer initiation. Crainbow fluorescent barcoding of wild-type HER2, d16-HER2, and p95-HER2 enables whole-gland lineage tracing and single-cell reconstruction of the origin of HER2+ breast cancer. Molecular pathology and Crainbow lineage tracing provide genotype:phenotype modules and gene signatures predictive of cancer progression. WT-HER2 neoplasms were rare and proliferative d16-HER2 neoplasms eventually progressed to metastasis, and p95-HER2 induced rapidly invasive and metastatic carcinomas. p95-HER2 carcinomas originate without detectable in situ stages – termed here a minimally detectable “nascent lethal carcinoma”. This nascent lethal program biases the commitment of tumor stem cells toward a metaplastic epithelial-mesenchymal transition-like (EMT) lineage promoting microenvironmental remodeling. Overall, these data suggest that lethality programs begin at initiation, indicating that detection must be improved to identify the nascent lethal lesion.
2021-05-31 | GSE152422 | GEO
Project description:Aberrant Notch signaling has been linked to many cancers including choroid plexus (CP) tumors, a group of rare and predominantly pediatric brain neoplasms. We developed animal models of CP tumors by inducing sustained expression of Notch1 that recapitulate properties of human CP tumors with aberrant NOTCH signaling. Whole transcriptome and functional analyses showed that tumor cell proliferation is associated with Sonic Hedgehog (Shh) in the tumor microenvironment. Unlike CP epithelial cells, which have multiple primary cilia, tumor cells possess a solitary primary cilium as a result of Notch-mediated suppression of multiciliate diffferentiation. A Shh-driven signaling cascade in the primary cilium occurs in tumor cells but not in epithelial cells. Lineage studies show that CP tumors arise from mono-ciliated progenitors in the roof plate characterized by elevated Notch signaling. Abnormal SHH signaling and distinct ciliogenesis are detected in human CP tumors, suggesting SHH pathway and cilia differentiation as potential therapeutic avenues.
2016-01-23 | GSE77123 | GEO
Project description:Creating spontaneous yet genetically tractable human tumors from normal cells presents a fundamental challenge. Retroviruses and transposons have been separately used as somatic cell insertional mutagens to identify cancer drivers in model organisms. Here we combined these mutagenic elements to enable cancer gene discovery starting with normal human cells. Lentivirus was used to seed gain- and loss-of-function gene disruption elements which were further deployed by Sleeping Beauty transposons throughout the genome of human bone explant mesenchymal cells. De novo tumors rapidly generated in this context were high-grade sarcomas corresponding to the spectrum of myxofibrosarcoma and undifferentiated pleomorphic sarcoma, aggressive neoplasms with a predilection for older adults. Tumor insertion sites were genome-wide and enriched in regions of recurrent somatic copy number alteration found in multiple cancers, with a bias towards those of sarcomas. Novel driver genes which sustain somatic alterations in cancer patients were pinpointed. We identify the gene HDLBP, which codes for the RNA binding protein vigilin, as a candidate tumor suppressor deleted at 2q37.3 in greater than one in ten tumors across multiple tissues of origin. Hybrid viral-transposon systems will accelerate the functional annotation of cancer genomes by enabling insertional mutagenesis screens in higher eukaryotes that are not amenable to germline transgenesis. Lentivirus was used to seed gain- and loss-of-function gene disruption elements which were further deployed by Sleeping Beauty (SB) transposons throughout the genome of human bone explant mesenchymal cells. Genomic locations of LV (lentiviral backbone) and SB insertion sites were mapped by a pooled strategy utilizing linear amplification mediated PCR (LAM-PCR), followed by Illumina next generation sequencing of the product pool.
2014-07-25 | E-GEOD-59720 | biostudies-arrayexpress
Project description:Creating spontaneous yet genetically tractable human tumors from normal cells presents a fundamental challenge. Retroviruses and transposons have been separately used as somatic cell insertional mutagens to identify cancer drivers in model organisms. Here we combined these mutagenic elements to enable cancer gene discovery starting with normal human cells. Lentivirus was used to seed gain- and loss-of-function gene disruption elements which were further deployed by Sleeping Beauty transposons throughout the genome of human bone explant mesenchymal cells. De novo tumors rapidly generated in this context were high-grade sarcomas corresponding to the spectrum of myxofibrosarcoma and undifferentiated pleomorphic sarcoma, aggressive neoplasms with a predilection for older adults. Tumor insertion sites were genome-wide and enriched in regions of recurrent somatic copy number alteration found in multiple cancers, with a bias towards those of sarcomas. Novel driver genes which sustain somatic alterations in cancer patients were pinpointed. We identify the gene HDLBP, which codes for the RNA binding protein vigilin, as a candidate tumor suppressor deleted at 2q37.3 in greater than one in ten tumors across multiple tissues of origin. Hybrid viral-transposon systems will accelerate the functional annotation of cancer genomes by enabling insertional mutagenesis screens in higher eukaryotes that are not amenable to germline transgenesis.
2014-07-25 | GSE59720 | GEO
Project description:The inference of genomic ancestry using ancestry informative markers (AIMs) can be useful for a range of studies in evolutionary genetics, biomedical research, and forensic analyses. However, the determination of AIMs for highly admixed populations with complex ancestries has remained a formidable challenge. Given the immense genetic heterogeneity and unique population structure of the Indian subcontinent, here we sought to derive AIMs that would yield a cohesive and faithful understanding of South Asian genetic origins. To discern the most optimal strategy for extracting AIMs for South Asians we compared three commonly used AIMs-determining methods namely, Infocalc, FST, and Smart Principal Component Analysis with ADMIXTURE, using previously published whole genome data from the Indian subcontinent. Our findings suggest that the Infocalc approach is likely most suitable for delineation of South Asian AIMs. In particular, Infocalc-2,000 (N = 2,000) appeared as the most informative South Asian AIMs panel that recapitulated the finer structure within South Asian genomes with high degree of sensitivity and precision, whereas a negative control with an equivalent number of randomly selected markers when used to interrogate the South Asian populations, failed to do so. We discuss the utility of all approaches under evaluation for AIMs derivation and interpreting South Asian genomic ancestries. Notably, this is the first report of an AIMs panel for South Asian ancestry inference. Overall these findings may aid in developing cost-effective resources for large-scale demographic analyses and foster expansion of our knowledge of human origins and disease, in the South Asian context.
| S-EPMC6143162 | biostudies-literature