News & Views

TGF-β can antagonise or cooperate with WNT signalling, yet it is still unclear what mechanisms integrate the outcomes of these conserved pathways. A new study now reports that the formation of biomolecular condensates, dependent on the DACT1 protein, provides the spatial segregation needed for TGF-β to constrain WNT signalling.

Facultative heterochromatin occurs at regions that contain developmentally regulated genes. A study now reveals that the nutrient-sensitive TORC1 signalling pathway affects the RNA elimination machinery, thereby regulating the timely expression of meiotic genes embedded in facultative heterochromatic loci.

Circular RNAs regulate a variety of biological processes. Now an unexpected pathway is revealed in which a translated circular RNA derived from E-cadherin pre-mRNA activates EGFR signalling in glioblastoma cancer stem cells and acts as a ligand for the EGFR mutant EGFRVIII, a common oncogenic variant.

Anorexia commonly develops in patients with advanced cancer and is closely associated with cachexia. A new study shows that anorexia emerges earlier than cachexia in both Drosophila and mouse tumour models and that tumour-derived humoral factors induce anorexia by systemically dysregulating neuropeptides in the brain.

Engineered, light-inducible artificial myosin motors enable selective and direct manipulation of filopodial extensions and provide refined tools to control intracellular cargo transport in vivo.

Prostate cancer is difficult to treat because of molecular, cellular and clinical heterogeneity. Using single-cell RNA sequencing, a recent study reveals unexpected transcriptomic reprograming in immune cells and non-immune components of the tumour microenvironment, which may lead to viable therapeutic approaches against prostate cancer.

Amino acids are critical nutrients that contribute to metabolic and signalling pathways required to meet energy and biosynthetic demands in T cells. A new study now demonstrates that LCK can sense intracellular asparagine to support T cell receptor-mediated CD8⁺ T cell activation and effector responses to pathogens and tumours.

Assembling egg cells involves cytoplasmic and nuclear processes that together enable embryonic development. A study now defines a set of transcription factors required for cytoplasmic, but not key nuclear, processes.

Nuclear dicing bodies were discovered in plants as subcellular droplets of a component of the Dicing complex, which is involved in microRNA production. Now they are revealed to be liquid–liquid phase-separated condensates with intrinsically disordered regions of the Dicing component SERRATE driving both phase separation and miRNA processing.

X-chromosome inactivation studies have revealed striking species specificities in terms of the players, kinetics and mechanisms. Transcriptomic profiling of human pre‐implantation development and germ cell differentiation suggests a peculiar dosage compensation mechanism with yet undefined contributions from XIST and XACT lncRNAs.

PI3K–Akt signalling downstream of cell-surface receptor activation has long been thought to occur at the plasma membrane. However, surprising evidence now reveals activation of PI3Kα-mediated PI(3,4,5)P₃ synthesis on endosomal membranes that is dependent upon the interaction of PI3Kα with the microtubule-associated protein MAP4.

There are many challenges in finding an effective, long-lasting and universal cure for the whole cohort of patients with Duchenne muscular dystrophy (DMD). The discovery of H19 lncRNA as a stabiliser of dystrophin may prove to be the missing link to the success of various rescue therapies proposed for treating DMD.

Triggering heart repair after myocardial infarction is a challenge in regenerative medicine. A study now shows how ERBB2-mediated YAP activation promotes both cardiomyocyte proliferation and epithelial-to-mesenchymal transition (EMT) in adult mice. EMT initiates cardiomyocyte dedifferentiation and migration and together with proliferation promotes cardiac regeneration.

Sirtuins are highly conserved enzymes with key roles in life extension in multiple organisms. A study now describes selective autophagic degradation of nuclear SIRT1 in senescent cells. These observations suggest that blocking sirtuin degradation could be a potential approach for anti-ageing therapies.

Protein homeostasis preserves stem cell function, but the underlying mechanisms are largely unknown. A study reveals that protein quality control mediated by the endoplasmic reticulum-associated degradation pathway ensures proper expression of MPL, a key cell surface receptor that promotes haematopoietic stem cell function through niche interaction.

Programmed death ligand-1 (PD-L1) is well known for its role as an immune checkpoint regulator, but little is known about its function in other cellular processes. A study now shows that in tumour cells PD-L1 mediates pyroptosis, an inflammatory form of cell death, by activating the expression of Gasdermine C, ultimately leading to tumour necrosis.

Ferroptosis is an iron-dependent mode of cell death driven by lipid peroxidation, capable of explosively propagating through a field of cells. Two studies now explore the mechanisms underlying ferroptotic cell death and its spread, as well as its possible in vivo significance, shedding light on some of the burning questions surrounding ferroptosis.

While the formation and concentration of urine are better understood, how kidney epithelial cells generate the energy to drive these functions has remained unclear. A study now reveals that shear stress originating from urinary flow is sensed by the primary cilia of cortical epithelial cells and stimulates lipolysis and oxidative metabolism.

PD-L1 has been extensively described as the membrane-bound ligand of PD-1. A recent study discovered a previously unknown role for PD-L1, which is able to bind DNA and thus govern different pathways linked to either evasion of immune surveillance or tumour microenvironment inflammation.

Studies of stem cell behaviour during regeneration have largely focused on understanding how cells make the choice between self-renewal and differentiation. It remains unclear whether cells undergo smooth transitions during differentiation or pause at selective intermediate states. Three studies now explore this question in lung regeneration.