Volume 25 Issue 1, January 2023

In type 2 diabetes, altered lipid metabolism causes a defect in insulin secretion. A study now shows how reduced very long-chain sphingolipids in β cells may impair the export of insulin-processing enzymes from the endoplasmic reticulum. The resulting defect in insulin production causes increased blood glucose concentrations.

The bone marrow is the daily production site for hundreds of billions of blood cells. A new study adds evidence that, during ageing, signals emanating from bone-marrow stromal cells shift to produce inflammatory factors that skew blood-cell output, driving age-related tissue deterioration.

End-binding proteins attach to the dynamic plus-ends of microtubules in order to regulate microtubule polymerization and the transport of other plus-end tracking proteins (+TIPs). Three new studies dissect the multivalent interactions that constitute distinct +TIP networks and reveal that they give rise to liquid-like biomolecular condensates.

Caveolin-1 (CAV1) is best known as a building block of caveolae, flask-shaped ‘little caves’ that buffer the plasma membrane by flattening in response to mechanical stress. CAV1 is now linked to a feature of cellular topography that can respond to mechanical cues and relieve membrane tension: dolines.

PD-1 and PD-L1 are important immune checkpoint molecules that modulate T cell activity. A study now shows that PD-1 marks leukaemia stem cells (LSCs) in T cell acute lymphoblastic leukaemia and reveals therapeutic opportunities to target LSCs via anti-PD-1 therapy.

Griess et al. determine the lipid signatures of pancreatic islets in type 2 diabetes models. They define a lipid environment linking the endoplasmic reticulum–Golgi transport protein Tmed2 to the proinsulin processing enzyme Pcsk1 to ensure insulin production.

Mitchell et al. identify reduced osteoprogenitors and increased mesenchymal stromal cells in old bone marrow niche, which creates an IL1-mediated inflammatory milieu that skews myeloid differentiation and impairs haematopoietic regeneration.

Yelagandula et al. show that ZFP462 interacts with G9A/GLP to modulate enhancers with binding sites for embryonic stem cell-specific transcription factors, thereby regulating lineage specification during neural differentiation of mouse embryonic stem cells.

Maan et al., Meier et al. and Song et al. report that microtubule plus-end binding proteins can undergo liquid–liquid phase separation to regulate microtubule dynamics.

Maan et al., Meier et al. and Song et al. report that microtubule plus-tip end binding proteins can undergo liquid–liquid phase separation and regulate microtubule dynamics.

Maan et al., Meier et al. and Song et al. report that microtubule plus-tip end binding proteins can undergo liquid–liquid phase separation and regulate microtubule dynamics.

Lee et al. uncover a previously uncharacterized role of OASL in virus-induced necroptosis. OASL chaperones the assembly of RIPK3 and ZBP1 via liquid-liquid phase separation, which induces RIPK3 and necroptosis activation, thereby modulating inflammation and host defence against viral infection.

Jung-Garcia et al. dissect the contributions of isoforms of the inner nuclear membrane protein LAP1 to nuclear envelope blebbing, constrained migration and invasion in melanoma cells.

Lolo et al. show caveolin-1 functions in non-caveolae structures termed dolines. Whereas caveolae respond to high forces over a mechanical threshold, dolines transduce low and medium mechanical forces gradually in a complementary buffering system.

Polycomb repressive complexes 1 and 2 both regulate maintenance of X inactivation in extra-embryonic lineages of post-implantation embryos by affecting overlapping yet different genes, thus implying potentially independent roles for the two complexes.

Cui et al. identify an important role for MLL3 in regulating the hybrid epithelial–mesenchymal transition state in breast cancer and show that deletion of MLL3 enhances metastatic capacity through increased IFNγ signalling.

Using somatic genome editing and Tuba-seq, Tang et al. uncover a previously uncharacterized role for HRAS and NRAS in impairing KRAS–KRAS interaction to suppress lung tumour growth.

Xu, Zhang, Xuan et al. show that PD-1 signalling defines a population of leukaemia stem cells with features of quiescence, drug resistance and protection against cell death, ablation of which suppresses disease progression of mouse and human T-ALL.

Stewart-Morgan et al. present isolation of DNA by 5-ethynyl-deoxyuridine labelling for mass spectrometry, a highly sensitive, quantitative mass spectrometry-based method for measuring DNA modifications on metabolically labelled DNA. They apply it to study DNA methylation and hydroxymethylation propagation.