TAK1 inhibition leads to RIPK1-dependent apoptosis in immune-activated cancers.

Poor survival and lack of treatment response in glioblastoma (GBM) is attributed to the persistence of glioma stem cells (GSCs). To identify novel therapeutic approaches, we performed CRISPR/Cas9 knockout screens and discovered TGFβ activated kinase (TAK1) as a selective survival factor in a significant fraction of GSCs. Loss of TAK1 kinase activity results in RIPK1-dependent apoptosis via Caspase-8/FADD complex activation, dependent on autocrine TNFα ligand production and constitutive TNFR signaling.

Histone editing elucidates the functional roles of H3K27 methylation and acetylation in mammals.

Posttranslational modifications of histones (PTMs) are associated with specific chromatin and gene expression states. Although studies in Drosophila melanogaster have revealed phenotypic associations between chromatin-modifying enzymes and their histone substrates, comparable studies in mammalian models do not exist. Here, we use CRISPR base editing in mouse embryonic stem cells (mESCs) to address the regulatory role of lysine 27 of histone H3 (H3K27), a substrate for Polycomb repressive complex 2 (PRC2)-mediated methylation and CBP/EP300-mediated acetylation.

MPP8 is essential for sustaining self-renewal of ground-state pluripotent stem cells.

Deciphering the mechanisms that control the pluripotent ground state is key for understanding embryonic development. Nonetheless, the epigenetic regulation of ground-state mouse embryonic stem cells (mESCs) is not fully understood. Here, we identify the epigenetic protein MPP8 as being essential for ground-state pluripotency.

Angiosarcoma at femoral artery puncture site; a diagnostic dilemma.

Femoral artery is the most common vascular access site used for angiographic interventions. Various complications such as hematoma, bleeding, dissection, arteriovenous fistula and pseudoaneurysm have been described following iatrogenic puncture. However, angiosarcoma formation at the access site is very uncommon and it poses a diagnostic dilemma due to its resemblance to organized hematoma.

Endogenous epitope-tagging of , and identifies TET2 as a naïve pluripotency marker.

, , and encode DNA demethylases that play critical roles during stem cell differentiation and reprogramming to pluripotency. Although all three genes are transcribed in pluripotent cells, little is known about the expression of the corresponding proteins. Here, we tagged all the endogenous family alleles using CRISPR/Cas9, and characterised TET protein expression in distinct pluripotent cell culture conditions.