Brad's Most Recent Paper of the Day

Category:   Wnt Signaling Stem Cells

An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control

Journal: Science.  Publication year: 2014

Although this review is now 6 years old, it still provides an excellent overview of the role of Wnt signaling in somatic stem cell control. The illustrations in this review are fantastic and provide a nice learning tool for those of us who are visual learners. Implications for Wnt signaling in the genesis of cancer are also described. For anyone studying Wnt signaling, this is a must read!

Category:   Development Cool Techniques

Multi-omics profiling of mouse gastrulation at single-cell resolution

Journal: Nature   Publication year: 2019

This is a fantastic resource for those studying early stages of development prior to, and during, gastrulation. Mouse embryos at stages E4.5, E5.5, E6.5 and E7.5 are analyzed by using single-cell multi-omics (MOFA) combining data from single-cell nucleosome, methylome and transcriptome sequencing. Key findings are that the early epiblastic cells have already been primed for ectodermal differentiation as determined by examining the methylation and accessibility of ectodermal promoters, whereas cells committed to mesodermal or endodermal differentiation undergo extensive coordinated chromatin remodelling in relevant enhancer regions.

Category:   Stem Cells Wnt Signaling

Functional Redundancy of GSK-3α and GSK-3β in Wnt/β-Catenin Signaling Shown by Using an Allelic Series of Embryonic Stem Cell Lines

Journal: Developmental Cell.   Publication year: 2007

This is another of my own papers from my time as a postdoc in the Woodget lab in Toronto. It was during this time that I became relatively adept at generating targeting constructs and using them to generate conditional knockout alleles introduced through homologous recombination in ES cells. Here, I described the phenotype of ES cells in which both GSK-3 genes (ɑ  and β) were knocked out. A key take-home message of the paper is that in Wnt/β-catenin signaling GSK-3ɑ and GSK-3β are interchangeable. Trust me, when you see GSK-3β depicted in the β-catenin destruction complex, this is incorrect! Unwarranted focus has been placed on GSK-3β  in many studies. When you are working on projects involving GSK-3 don't forget about GSK-3ɑ!

Category:   Development Wnt Signaling Cancer

Role of Glycogen Synthase Kinase-3 in Cell Fate and Epithelial-Mesenchymal Transitions

Journal: Cells Tissues Organs   Publication Year: 2007

This is a review I wrote when I was a postdoc in Jim Woodgett's lab. For those unfamiliar with epithelial-to-mesenchymal transitions (EMT), or the reverse process of mesenchymal-to-epithelial transitions (MET) , this review is a nice short basic primer. My interest in EMT/MET has recently been renewed, so I've been delving back into the literature myself. One of the reasons I am fond of this particular review is because of my depictions of slug and snail, which add a bit of humour to the figure of the pathways involved. I especially had fun rendering slug, although it ended up being more of a sea slug variety. If I had to illustrate slug again, it would have two protruding tentacles, like common garden slugs.

Category:   Running a Lab

Mole's Wow! So now you have your own lab!

Journal: Journal of Cell Science   Publication Year: 2015

This is not a research paper, and although the subject matter is presented in cartoon form, this comic strip series is an excellent resource for new investigators. Through depictions of typical scenarios that occur throughout one's career as a biomedical scientist, Mole provides much sage advice. This comic is also great for those hoping to pursue a career as a biomedical scientist and those who have no idea what such a career entails.

Category:   Cool Techniques

Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors

Journal: Nature Biotechnology  Publication Year: 2020

Here's the first paper I've selected as Brad's Paper of the Day. The authors use elegant screens in bacterial and mammalian cells to improve the on-target efficiency of cytosine base editors. For those who haven't been following CRISPR/Cas9 technology, base editors employ an engineered fusion protein comprising cytidine deaminase linked to a Cas9 nickase protein and multiple copies of a uracil glycosylase inhibitor (UGI). When the synthetic editor complex is directed to a target C·G base pair by an sgRNA, it is converted to a T·A base pair. The screens used by the Liu lab resulted in optimized base editors with 10- to 100-fold reduction in off-target editing.

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