News & Views

Tumour-secreted microvesicles carry bioactive molecules that can be transferred to recipient cells, impacting tumour progression. A study now shows that ARF6 drives miRNA loading into tumour microvesicles through interaction with pre-miRNA–Exportin-5 complexes, thus shedding light on specific cargo packaging mechanisms.

Centromere identity must be maintained through multiple generations. A new study reveals a Constitutive Centromere-Associated Network (CCAN)-dependent retention of CENP-A, a key epigenetic mark for centromeres, in centromeres during DNA replication and a replication-dependent error correction to eliminate ectopic CENP-A in chromosome arms.

Embryonic stem cells derived from the inner cell mass can differentiate to all embryonic lineages of any adult cell type and to a limited extent to extra-embryonic tissues. A study now allows the generation of pig and human stem cells with enhanced differentiation potential towards all embryonic and extra-embryonic fates, one step closer to the totipotent state of the fertilized egg.

IRE1α is an endoplasmic reticulum (ER) transmembrane protein known for a crucial role in regulating the unfolding protein response. A study now shows that IRE1α interacts with the main ER Ca²⁺ channel InsP₃Rs and facilitates the transfer of Ca²⁺ from the ER into mitochondria, thus driving cellular metabolism.

Yap signalling is crucial for intestinal regeneration, but its role is largely dispensable in homeostasis. Two studies now reveal Yap-dependent mechanisms of intestinal regeneration and tissue organization: transient expansion of a rare cell type after damage in vivo and Notch–Dll activation for symmetry breaking in organoid development.

Haematopoietic stem cells (HSCs) are maintained in vivo by intrinsic programs and extrinsic niche signals. Ex vivo expansion of HSCs is limited, owing to reduced stem cell maintenance factors. A study now shows that rejuvenated niche cells can be obtained by transcriptional rewiring of specific genes that maintain and expand HSCs ex vivo.

Rag GTPases play a crucial role in mTORC1 activation by promoting its recruitment to the lysosomal surface in a nutrient-dependent manner. A study now identifies a family of lysosomal G-protein-coupled receptors as modulators of Rag GTPases localization and activation, adding one more component to the fast-growing mTOR regulatory network.

Components of the spliceosome are frequently mutated in haematopoietic malignancies. Identification of mis-spliced genes promoting transformation will uncover novel targeted therapies. Now, a long isoform of IRAK4 is shown to be upregulated in a subset of acute myeloid leukaemia patients, conferring susceptibility for IRAK4 inhibition therapy.

MicroRNAs (miRNAs) repress target mRNAs, often with exquisite tissue specificity. Wang et al. exploit the specific expression of miRNAs to regulate guide production for Cas9. Their method enables novel strategies to simultaneously measure the activity of multiple miRNAs and restrict Cas9 binding or genome editing to precisely defined cell types.

HIV particles incorporate host membrane proteins into their envelope to evade the immune system and infect other cells. A study now shows that Gag assembly on the host cell membrane produces a raft-like nanodomain favourable for protein partitioning due to a transbilayer coupling mechanism assisted by long saturated chain lipids and cholesterol.

Osteoclasts are known for their role in bone resorption. A study now shows that a vascular–associated osteoclast subtype at the growth plate also regulates blood vessel growth in bone and is supported by type H endothelial cells. These type H capillaries, in turn, release proteinases that promote cartilage degradation.

Macrophages modulate mammary tumour response to chemotherapy. A new study shows that targeted elimination of macrophages elicits a type I interferon response in the tumour microenvironment that enhances the efficacy of platinum- but not taxane-based chemotherapy, underscoring complex regulatory roles for macrophages in chemotherapy-treated tumours.

Epithelial–mesenchymal transition (EMT) is crucial for development, and for dissemination and invasion of cancer cells. A study now identifies the apical–basolateral polarity status of epithelia as a checkpoint for EMT induction and tumour metastasis through aPKC–Par3-regulated degradation of the EMT transcription factor SNAI1.

Healthy and malignant haematopoietic stem cells (HSCs) must overcome a variety of cell intrinsic and extrinsic stresses to maintain their functionality. Now, IRE1α –XBP1 signalling is shown to protect HSCs and to promote survival of, and confer competitive advantages to, NRAS-mutated pre-leukaemic cells.

Cell metabolism ensures that cell dynamics and continued renewal are supported by a constant flow of matter that consumes energy. A new study shows that cell metabolism is sensitive to mechanical cues, revealing that the level of cell contraction modulates the production and storage of lipids, which could serve as fuel for energy production.

Patients with diabetes could benefit from cell-based insulin therapy, but the supply of human islet tissue is limited. A study now reports an approach in which human-pluripotent-stem-cell-derived islet β-cells are purified and re-aggregated to generate cells that more closely resemble mature human β-cells.

AKT, also known as protein kinase B, is one of the most frequently dysregulated serine/threonine kinases in cancer, and its hyperactivity drives tumorigenesis and chemotherapy resistance. Two studies now find that AKT methylation by the methyltransferase SETDB1 is an early step in its oncogenic activation.

Stressed eukaryotic cells store mRNAs in protein-rich condensates called stress granules. Using single-molecule tracking techniques to examine how mRNAs enter stress granules, a new study shows that mRNAs make transient contacts with the granule surface before stable association, and become largely immobile after entry.

It is commonly accepted that disseminated tumour cells survive cytotoxic chemotherapy because they are not proliferating. A new study now finds that, in contrast to this long-standing concept, both dormant and proliferative cancer cells can be protected from chemotherapy when they reside at the perivascular niche.

Ancestral experience of mitochondrial stress is now found to render progeny of the roundworm Caenorhabditis elegans more resistant to the same insult for up to four generations. A DNA modification, N6-methyldeoxyadenine, is implicated in the inheritance of this stress adaptation.