Volume 23 Issue 7, July 2021

Intestinal organoids have been used to model development of the crypt–villus axis and uncover signalling pathways that govern the stem-cell niche and induce differentiation. Two studies now take advantage of intestinal organoids to measure the mechanical forces that drive morphogenesis of the crypt and fate specification of its resident cells.

A form of programmed cell death, necroptosis, in intestinal epithelial cells initiates mucosal inflammation. A study now finds that prostanoid EP4 receptor signalling interferes with RIPK1–RIPK3-dependent MLKL activation, thereby inhibiting necroptosis and accelerating resolution of inflammation.

A new study shows that the SARS-CoV-2 nucleocapsid protein represses the antiviral type I interferon response through direct interaction with the signalling adaptor protein MAVS. Targeting this process might be a useful therapeutic strategy to boost immunity against COVID-19.

Zhang et al. identify ALKBH7 as the demethylase of mitochondrial pre-tRNAs that regulates nascent mitochondrial RNA processing and translation. ALKBH7 loss impairs mitochondrial functions including fatty acid oxidation, leading to obesity.

Scheibner et al. demonstrate that, during gastrulation in the mouse, epithelial epiblast progenitors upregulate Foxa2 and form the definitive endoderm independently of a full EMT–MET cycle.

Clapes et al. show that chemotherapy leads to chromatin reorganization and increased expression of transposable elements, which promote an MDA5-driven inflammatory response that enhances haematopoietic regeneration.

Wang et al. report that the nucleocapsid protein of SARS-CoV-2 forms phase-separated condensates to repress K63-linked ubiquitination and aggregation of mitochondrial antiviral-signalling protein, thus suppressing antiviral immunity.

Yang, Xue et al. demonstrate in intestinal organoids that region-specific cell fates drive actomyosin patterns and modulate luminal osmotic forces to coordinate morphogenesis.

Pérez-González et al. explore the mechanical properties of intestinal organoids, and report the existence of distinct mechanical domains and that cells are pulled out of the central crypt along a gradient of increasing tension.

Wang et al. identify CCM3 as a negative regulator of YAP/TAZ activation and mechanotransduction in focal adhesions, with important roles in controlling mesenchymal/stromal stem cell differentiation and metastasis in mouse models of breast cancer.

Koester et al. show that, as hair follicle stem cells age, their ability to activate bivalent genes for self-renewal and differentiation is reduced due to increased niche stiffening and subsequent epigenetic effects.

Gong et al. uncover a role for the Golgi network in ER-associated endosome fission, showing that a Golgi-derived SEC14L2 compartment mediates ER-associated endosome fission by promoting PtdIns4P to PtdIns3P conversion.

Patankar et al. identify E-type prostanoid receptor 4 as a negative regulator of tumour necrosis factor signalling and mixed-lineage kinase domain-like pseudokinase activation, thereby suppressing necroptosis of intestinal epithelial cells and promoting resolution of intestinal inflammation.