Targeted mutagenesis recapitulates brain tumor initiation in cerebral organoids (RNA-seq data set: 130d)
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PROVIDER: PRJNA434108 | ENA |
REPOSITORIES: ENA
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Project description:Targeted mutagenesis recapitulates brain tumor initiation in cerebral organoids
| PRJNA434103 | ENA
Project description:Introduction of brain tumor-relevant genetic aberrations initiates different subtypes of brain tumor-like neoplasms in cerebral organoids
2018-05-30 | GSE101577 | GEO
Project description:Introduction of brain tumor-relevant genetic aberrations initiates different subtypes of brain tumor-like neoplasms in cerebral organoids
2018-05-30 | GSE110610 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-05-30 | GSE110611 | GEO
Project description:Targeted mutagenesis recapitulates brain tumor initiation in cerebral organoids (RNA-seq data set: 45d)
| PRJNA394872 | ENA
Project description:The CRISPR-Cas9 system enables efficient sequence-specific mutagenesis for creating germline mutants of model organisms. Key constraints in vivo remain the expression and delivery of active Cas9-guideRNA ribonucleoprotein complexes (RNPs) with minimal toxicity, variable mutagenesis efficiencies depending on targeting sequence, and high mutation mosaicism. Here, we established in vitro-assembled, fluorescent Cas9-sgRNA RNPs in stabilizing salt solution to achieve maximal mutagenesis efficiency in zebrafish embryos. Sequence analysis of targeted loci in individual embryos reveals highly efficient bi-allelic mutagenesis that reaches saturation at several tested gene loci. Such virtually complete mutagenesis reveals preliminary loss-of-function phenotypes for candidate genes in somatic mutant embryos for subsequent generation of stable germline mutants. We further show efficient targeting of functional non-coding elements in gene-regulatory regions using saturating mutagenesis towards uncovering functional control elements in transgenic reporters and endogenous genes. Our results suggest that in vitro assembled, fluorescent Cas9-sgRNA RNPs provide a rapid reverse-genetics tool for direct and scalable loss-of-function studies beyond zebrafish applications.
2016-05-01 | E-MTAB-4143 | biostudies-arrayexpress
Project description:Development of multicellular organisms proceeds via the correct interpretation of positional information to establish boundaries that separate developmental fields with distinct identities. The maize leaf is an ideal system to study plant morphogenesis as it is subdivided into a proximal sheath and a distal blade, each with distinct developmental patterning. Specialised ligule and auricle structures form at the blade-sheath boundary. The auricles act as a hinge, allowing the leaf blade to project at an angle from the stem, while the ligule comprises an epidermally-derived fringe. Recessive liguleless1 mutants lack ligules and auricles, and have upright leaves. We utilized laser-microdissection RNAseq to identify genes that are differentially expressed along discrete cell/tissue-specific domains along the proximal-distal axis of wild-type leaf primordia undergoing ligule initiation, and compared transcript accumulation in wild type and liguleless1 mutant leaf primordia. We identified transcripts that are specifically upregulated at the blade-sheath boundary. A surprising number of these ligule genes are also implicated to function during leaf initiation or lateral branching, and intersect multiple hormonal signalling pathways. We propose that genetic modules utilised in leaf and/or branch initiation are redeployed to regulate ligule outgrowth from leaf primordia. In this study, we analysed the transcriptome associated with ligule formation using laser microdissection RNA-sequencing (LM-RNAseq). We quantified transcript accumulation in the PLB and adjacent pre-blade and pre-sheath regions of wild-type leaf primordia in order to identify candidate genes involved in proximal-distal patterning at the blade-sheath boundary. We also compared transcript accumulation in lg1-R mutants and wild-type siblings to identity genes acting downstream of LG1.
2014-09-12 | E-GEOD-61333 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25636: A mouse model of deregulation of the malt1 oncogene recapitulates the pathogenesis of human malt lymphoma [MouseSca1 dataset] GSE25637: A mouse model of deregulation of the malt1 oncogene recapitulates the pathogenesis of human malt lymphoma [Spleen dataset] GSE25638: A mouse model of deregulation of the malt1 oncogene recapitulates the pathogenesis of human malt lymphoma [MALT dataset] Refer to individual Series
2012-07-09 | E-GEOD-25639 | biostudies-arrayexpress
Project description:Development of multicellular organisms proceeds via the correct interpretation of positional information to establish boundaries that separate developmental fields with distinct identities. The maize leaf is an ideal system to study plant morphogenesis as it is subdivided into a proximal sheath and a distal blade, each with distinct developmental patterning. Specialised ligule and auricle structures form at the blade-sheath boundary. The auricles act as a hinge, allowing the leaf blade to project at an angle from the stem, while the ligule comprises an epidermally-derived fringe. Recessive liguleless1 mutants lack ligules and auricles, and have upright leaves. We utilized laser-microdissection RNAseq to identify genes that are differentially expressed along discrete cell/tissue-specific domains along the proximal-distal axis of wild-type leaf primordia undergoing ligule initiation, and compared transcript accumulation in wild type and liguleless1 mutant leaf primordia. We identified transcripts that are specifically upregulated at the blade-sheath boundary. A surprising number of these ligule genes are also implicated to function during leaf initiation or lateral branching, and intersect multiple hormonal signalling pathways. We propose that genetic modules utilised in leaf and/or branch initiation are redeployed to regulate ligule outgrowth from leaf primordia.
2014-09-12 | GSE61333 | GEO
Project description:The sources of genome instability, a hallmark of cancer, remain incompletely understood. One potential source is DNA re-replication, which arises when the mechanisms that prevent re-initiation of replication origins within a single cell cycle are compromised. Using the budding yeast Saccharomyces cerevisiae, we previously showed that DNA re-replication is extremely potent at inducing gross chromosomal alterations and that this arises in part because of the susceptibility of re-replication forks to break. Here, we examine the ability of DNA re-replication to induce nucleotide level mutations. During normal replication these mutations are restricted by three overlapping error avoidance mechanisms: the nucleotide selectivity of replicative polymerases, their proofreading activity, and mismatch repair. Using lys2InsEA14, a frameshift reporter that is poorly proofread, we show that re-replication induces up to a 30x higher rate of frameshift mutations and that this mutagenesis is due to passage of the re-replication fork, not secondary to re-replication fork breakage. Re-replication can also induce comparable rates of frameshift and base substitution mutations in a more general mutagenesis reporter CAN1, when the proofreading activity of DNA polymerase ε is inactivated. Finally, we show that the induction of lys2InsEA14 frameshift mutations by re-replication is dependent on mismatch repair. These results suggest that the mismatch repair associated with re-replication is attenuated, although at most sequences DNA polymerase proofreading provides enough error correction to mitigate the mutagenic consequences. Thus, re-replication can facilitate nucleotide level mutagenesis in addition to inducing gross chromosomal alterations, broadening its potential role in genome instability.
2018-12-27 | GSE124382 | GEO