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Genetic screening for single-cell variability modulators driving therapy resistance [WM989-A6-G3-Cas9 5a3]

ABSTRACT: We present the transcriptome of WM989-A6-G3-Cas9 5a3 melanoma cells followng the knockout (via CRISPR-Cas9) of different proteins we identified as modulators the frequency of cellular states associated with resistance to mutant-BRAF inhibition therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE151825 | GEO | 2020/06/05

REPOSITORIES: GEO

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Genetic screening for single-cell variability modulators driving therapy resistance [WM989-A6-G3-Cas9 5a3]

Project description:Genetic screening for single-cell variability modulators driving therapy resistance [WM989-A6-G3-Cas9 5a3]

| PRJNA637377 | ENA

clampFISH 2.0 enables rapid, scalable amplified RNA detection in situ

Project description:We developed an amplified single-molecule RNA FISH method called clampFISH 2.0. To validate its performance, we used clampFISH 2.0 on two cell lines, WM989 A6-G3 cells and WM989 A6-G3 cells grown in vemurafenib, and across 10 genes, compared clampFISH 2.0 spot counts to the FPKM values from bulk RNA sequencing.

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Regulation of somatosensory mechanotransduction by Annexin A6

Project description:Sensory neuron mechanically-activated slowly adapting currents have been linked to noxious mechanosensation. We identified a Conotoxin, Noxious Mechanosensation Blocker -1, that blocks such currents selectively. Using an active biotinylated form of the toxin we identified 67 binding proteins in sensory neurons and sensory neuron-derived cell lines using mass spectrometry. Annexin A6 was the most frequently identified binding protein. Annexin A6 knockout mice showed an enhanced sensitivity to mechanical stimuli. Rapidly adapting currents were enhanced and slowly adapting channels diminished. The percentage of neurons expressing slowly adapting currents fell and non-responsive neurons increased. Conversely, overexpression of annexin A6 in DRG neurons inhibited rapidly adapting currents without effects on slowly adapting currents. Co-expression of annexin A6 with Piezo 2 led to an inhibition of Piezo-mediated rapidly adapting currents. AAV-mediated gene delivery of annexin A6 to sensory neurons in a mouse model of osteoarthritis attenuated mechanical pain. These data demonstrate a role for annexin A6 in somatosensory mechanotransduction.

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Lysobacter sp. A6 strain:A6

Project description:Lysobacter sp. A6 strain:A6 Genome sequencing and assembly

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Genetic screening for single-cell variability modulators driving therapy resistance

Project description:We present the transcriptome of WM989 melanona cells without or without inhibition of DOT1L. Different samples represent either the bulk population of melanoma cells, or subpopulations that express high or low levels of the drug resistance markers EGFR and NGFR

2020-04-25 | GSE149280 | GEO

Transcription profiling of hind limbs from annexin A5 and A6 knock-out mice

Project description:Initiation of mineralisation during endochondral ossification is a multistep process and was assumed to correlate with specific interactions of annexins and collagens. Annexins A5 and A6 are postulated to represent the essential annexins promoting cartilage mineralisation. However, skeletal development appears to be normal in annexin A5 or A6 deficient mice. The highly conserved structures of annexins led to the assumption that annexins A5 and A6 may fulfill redundant functions. We now generated mice deficient for both proteins, annexins A5 and A6. Mice were viable, fertile and showed no obvious abnormalities. Assessment of skeletal elements using histological, ultrastructural and peripheral quantitative computed tomography methods revealed that mineralisation and development of the skeleton was not significantly affected in mutant mice. In respect of the lack of an obvious phenotype we now applied microarray analysis to the growth plate to define changes in the transcriptome of juvenile murine growth plates from mutant mice. Global gene expression analysis revealed subtle phenotypes at the transcriptome level of genes involved in cell growth and intermediate metabolism in mutant mice. These data demonstrate that both annexins are dispensable for proper cartilage mineralisation but may affect cell proliferation processes at the transcriptomic level.

2009-02-17 | E-MEXP-1718 | biostudies-arrayexpress

Coxsackievirus A6

Project description:Coxsackievirus A6 Raw sequence reads

| PRJNA345653 | ENA