Reviews & Analysis

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.

The intestinal stem cell niche McCarthy, Kraiczy and Shivdasani review the cellular and molecular organisation of the mammalian intestinal stem cell niche and its functions.

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.

Cellular plasticity allows tumours to adapt to and overcome therapeutic challenges. A recent study uncovered the gene regulatory networks that govern cell states and phenotype switching in melanoma, opening up possibilities to therapeutically target cell states or phenotypic plasticity to render melanoma cells more vulnerable to treatment.

In this issue of Nature Cell Biology, Mercier et al. show that acute changes in membrane tension may be a physiological trigger for ESCRT assembly, which drives membrane scission, luminal vesicle budding, and a wide array of other membrane remodelling events throughout the cell.

There is increasing appreciation that many proteins self-aggregate in cells to form functional subcompartments, some of which exist as a separate liquid phase. A study now identifies the biophysical properties of AKAP95 protein condensates as critical for supporting cancer cell proliferation and RNA splicing.

Secretory proteins undergo multiple rounds of co- and post-translational quality control checks inside the cell, but how their integrity is maintained outside the cell is an emerging topic. A study establishes a model system to investigate how the extracellular proteome is protected and integrates its findings into existing immune pathways.

Cellular senescence has been widely recognised for decades as a stable arrest of cell proliferation. A recent study identifies senescence establishment and maintenance as a dynamic and reversible process regulated by (in)activation of a predetermined enhancer landscape controlled by the pioneer transcription factor AP-1.

Stem cells tightly link their metabolism to cell fate decisions; however, how cancers co-opt and bypass metabolic pathways for growth advantage remains unclear. New evidence in this issue highlights how cancer stem cells avoid epigenetically driven differentiation by shutting down endogenous serine synthesis and becoming serine auxotrophs.

The transcription factor oestrogen receptor alpha (ERα) has long been targeted for therapeutic benefit in cancer, but drug resistance can emerge through a multitude of mechanisms. A study now reveals how the ERα cistrome can become reprogrammed to confer resistance to tamoxifen in breast cancer.