Read the Publication This week we profile a recent publication in eLife from Dr. Parisa Asghari (pictured) the laboratory of Dr. Edwin Moore at UBC. Can you provide a brief overview of your lab’s current research focus? The Moore lab is studying the mechanisms which control excitation-contraction coupling in muscle cells. What is the significance of the findings in this publication? Dysfunctional…
The role of low oxygen in early placental development is controversial and inconclusive. The authors integrated advanced placental cell cultures exposed to low, moderate and high levels of oxygen with non-biased conventional transcriptomic and single-cell transcriptomic approaches. They showed that exposure to low oxygen conditions promoted the differentiation of primitive trophoblasts toward advanced invasive cell types, while culture in high oxygen conditions slowed this process.
We and others recently showed that coordinated expression of long non-coding RNAs (lncRNAs) is essential for myeloid differentiation and that, in turn, deregulation of lncRNAs contributes to the pathogenesis of AML1. To better understand the relationship between lncRNAs that control granulopoiesis and the block of differentiation in AML blasts, we sequenced stranded, non-poly-A-enriched cDNA libraries that were prepared from healthy…
When neurons extend their processes, they often make excessive number of neurites at early stages of development. Later, unnecessary neurites are removed by neurite pruning. The authors report that the neurite pruning is regulated by a secreted protein, Wnt, and its receptor protein, Frizzled. Using genetic approaches including CRISPR/Cas9 genome editing technology, they found that neurite pruning is induced only when the neurites are in close proximity to the cells expressing Wnt.
The regulatory approval of Onpattro, a lipid nanoparticle-based short interfering RNA drug for the treatment of polyneuropathies induced by hereditary transthyretin amyloidosis, paves the way for clinical development of many nucleic acid-based therapies enabled by nanoparticle delivery.
The authors examined mesenchymal progenitors (MP) in skeletal muscle regeneration, showing that they play several critical roles important for muscle regeneration. They reported that MPs directly contribute to regeneration of various connective tissue structures, including the myotendinous junction, and identified a subpopulation of MPs that directly regenerates this structure. Collectively, the results in the paper define a number of important activities of MPs in skeletal muscle regeneration.
High YAP activity is associated with poor prognosis human breast cancers, but its role during the initial stage of mammary cell transformation is unknown. To address this question, we designed experiments that exploit the ability of KRASG12D-transduced subsets of freshly isolated normal human mammary cells to form invasive tumors rapidly and efficiently when transplanted into immunodeficient mice. Initial examination of the…
The authors have found that ELF3, a transcription factor, is a new amplified oncogene in approximately 80% of all lung adenocarcinomas (LUAD), the largest subtype of lung cancer. Using a mouse model, they have found that LUAD cells that express ELF3 are selected for in implanted tumours, and ELF3 expression is required for tumour growth. They also saw that in human LUAD tumours, high expression of ELF3 is associated with poor patient outcome, indicating the importance of ELF3 to LUAD biology.
The authors used an automated tracking system to quantify 26 measures spanning morphology, locomotion, tactile sensitivity and habituation learning in 135 strains of C. elegans, each carrying a mutation in a gene associated with autism spectrum disorder. They found that loss of function mutations in many of these genes delayed development, and that many of the genes impaired the animal’s ability to habituate. The result was that many of the strains kept responding to sensory stimuli when they should have learned to stop.
It has been shown that metastatic prostate cancers with mismatch repair defects are likely to respond to immune checkpoint inhibition, a class of therapy that has little efficacy in unselected patients. The authors demonstrated that mismatch repair defective metastatic prostate cancer can be identified and characterized using plasma circulating tumour DNA. They showed that it is not strictly necessary to identify the precise underlying defect because the signature of high tumour mutational burden and microsatellite instability can manifest at the genome-wide level, even in a liquid biopsy.