Volume 21 Issue 11, November 2019

Pancreatic ductal adenocarcinoma displays high levels of cellular heterogeneity, which is associated with drug resistance and high metastatic rates. A new study shows that tetraspanin CD9 marks PDAC tumour-initiating cells and functions as a regulator of glutamine metabolism.

PTEN is a phosphatase that functions as a tumour suppressor by antagonizing the PI3K–AKT pathway. However, a study now demonstrates that translational variants of PTEN enable new interactions between PTEN and the COMPASS complex, identifying a new role for PTEN in modifying gene expression via COMPASS-mediated histone H3 lysine 4 methylation.

Saçma, Pospiech and co-workers show that sinusoidal niches are uniquely preserved on ageing, that they are the predominant niche for label-retaining (LR)-HSCs in aged mice and display higher reconstitution capacity compared with non-LR HSCs.

Aloia, McKie, Vernaz et al. show that during liver damage ductal cells acquire cellular plasticity by undergoing epigenetic remodelling, with TET1-mediated regulation of ErbB–MAPK and YAP–Hippo signalling.

Yvernogeau, Gautier, Petit et al. demonstrate the existence of a haemogenic endothelium capable of de novo haematopoietic stem and progenitor cell generation in the forming bone marrow of chicken and mouse fetuses and newborns.

Wang et al. identify ZNFX1 as a mitochondria-localised sensor that recognizes viral dsRNA and induces a type I interferon response, thereby restricting virus infection.

Jaumouillé et al. show that a talin/vinculin-based molecular clutch mechanically couples the forces generated by Arp2/3- and Dia1-mediated actin polymerization to promote integrin-mediated phagosome formation.

Yolland et al. demonstrate persistent flow of the actin flow behind the leading edge and its impact on cell directionality during migration.

By measuring metabolic and biosynthetic activity with cell cycle progression, Litsios et el. uncover pulses in protein production rate that do not scale with cell size but drive cell cycle entry in budding yeast.

Abramo et al. show that during mitosis, condensin-mediated loops are lost by telophase and a transient chromosome folding intermediate is formed that lacks cohesin-generated loops.

Rodrigues et al. show that exosomal CEMIP derived from brain metastatic cells elicits vascular remodelling and inflammation and supports subsequent metastatic colonization in the brain microenvironment.

Schmidt et al. show that the translation initiation factor eIF2B5 regulates stress responses and MYC translation to prevent apoptosis, thereby presenting a targetable vulnerability in colorectal cancer.

Wang et al. demonstrate that CD9 marks tumour-initiating cells in pancreatic ductal adenocarcinoma (PDAC), and enhances glutamine uptake to promote tumour development in vivo that recapitulates the cellular heterogeneity of primary PDAC.

Shen et al. show that PTENα/β stability is regulated through a ubiquitin-dependent mechanism mediated by USP9X and FBXW11 to modulate H3K4 trimethylation through WDR5 and promote tumour development.

Brumbaugh, Kim et al. generate mice with inducible H3 K-to-M mutations, which globally inhibit methylation at specific sites, and analyse specific phenotypes and changes in chromatin accessibility and transcriptional programmes.