News & Views

The molecular clock regulates the rhythmic transcription of myriad genes, leading to a circadian pattern of expression of the encoded proteins. A study demonstrates circadian regulation of expression of components of the protein secretory pathway, providing a mechanism to generate circadian patterns of secreted protein expression.

Different types of stromal cells in the bone marrow associate to form niches that support differentiating blood cells and ensure lifelong production of all major blood lineages. A study now combines single-cell and spatial transcriptomics with imaging to infer the cellular composition and spatial architecture of specific niches.

Tangential expansion of neural stem cells in the mammalian neocortex increases the number of cortical columns. A new study shows that neural stem cells that become detached from the apical surface during division regenerate an apical endfoot to ensure tangential expansion in the early stage but later lose this ability when radial expansion occurs.

Tendons have limited regenerative potential, and injuries often cause scarring. A study now identifies a tendon stem cell population that contributes to regeneration and a tendon fibro–adipogenic progenitor population involved in fibrosis.

In mammals, a circadian timing system composed of a master clock in the brain’s suprachiasmatic nucleus and oscillators in peripheral organs drives daily rhythms of behavior and physiology. A study now reveals that the periodic oxidation of the CLOCK protein enhances the amplitude of cyclic gene expression and affects the daily rhythms of behavior.

Pancreatic ductal adenocarcinoma displays high levels of cellular heterogeneity, which is associated with drug resistance and high metastatic rates. A new study shows that tetraspanin CD9 marks PDAC tumour-initiating cells and functions as a regulator of glutamine metabolism.

After mitosis chromosomes are drastically reshaped. A study now charts the dynamics of this conformational change at high temporal resolution. During the shift from one loop-forming complex (condensin) to another (cohesin), an intermediate chromosome folding state exists in which neither of these complexes are associated with chromatin.

PTEN is a phosphatase that functions as a tumour suppressor by antagonizing the PI3K–AKT pathway. However, a study now demonstrates that translational variants of PTEN enable new interactions between PTEN and the COMPASS complex, identifying a new role for PTEN in modifying gene expression via COMPASS-mediated histone H3 lysine 4 methylation.

The non-specific lethal (NSL) complex is a highly conserved MOF acetyltransferase-containing complex. A recent study now shows that the NSL complex acetylates a new non-histone target, Lamin A/C and reveals the NSL complex as a crucial factor in maintaining nuclear architecture and genome integrity.

Endosomes are central stations for converging proteins from biosynthetic pathways and endocytic routes. Many endosomal proteins are sorted to the plasma membrane or the Golgi despite the lysosome being the primary endosomal fate. SNX5 and SNX6 are now revealed to decode a conserved bipartite signal to mediate protein sorting to the Golgi or the plasma membrane.

Cell identity is shaped by a complex interplay between transcription factors, enhancers and genome organisation. A study now reveals a dynamic role for the transcription factor KLF4 in directing gene regulatory interactions during pluripotent cell reprogramming, demonstrating that transcription factors can function as chromatin organisers.

Assembly of the mitotic spindle requires timely separation of the centrosomes. Their movement apart is driven by the plus-end-directed kinesin Eg5. A new study demonstrates that the kinesin KIFC3 provides an opposing microtubule-based cohesive force that modulates centrosome separation and ensures accurate chromosome segregation.

Tumours elicit an immune attack that can stifle their growth, but they can also recruit inflammatory immune cells that suppress this response. A new study identifies distinct immune subtypes of triple-negative breast cancer with two different inflammatory cell types: macrophages or neutrophils. The immune subtype dictates the response to immunotherapy.

Activation of the receptor EGFR (ERBB1) occurs in response to viral infections and regulates antiviral immunity. A new study now shows that the receptor HER2 (ERBB2) negatively regulates STING signaling in response to DNA viruses and expands the model and mechanisms by which surface-receptor tyrosine kinases perform important intracellular regulatory functions.

Migrasomes are a recently discovered type of extracellular vesicles that are characteristically generated along retraction fibers in migrating cells. Two studies now show how migrasomes are formed and how they function in the physiologically relevant context of the developing zebrafish embryo.

Loss-of-function mutations in the ubiquitin ligase Parkin are a cause of Parkinson’s disease. Parkin also has tumour-suppressor activity, although how Parkin prevents cancer is unclear. Unexpectedly, Parkin is found to suppress cancer by inhibiting an inflammatory type of cell death called necroptosis.

Tissue renewal requires proliferative progenitors with long-lasting potential. Designated stem cells within specialized niches are considered to be the primary mechanism for this requirement. Recent studies show that dispersed equipotent progenitors are sufficient to account for fast-paced cellular dynamics in skin oil glands and foetal gut epithelium.

The ability of cancer cells to adapt to external and internal stresses is critical for tumourigenesis. A new study now shows that the integrated stress response is critical for tumour cell adaptation to stress induced by c-MYC activation, providing mechanistic insights into tumour responses to intrinsic stresses with implications for cancer therapies.

Different subclones cooperate to support tumour heterogeneity and growth, but the effect on metastasis is unclear. A new study now shows that, as non-cell-autonomous drivers, minor cancer cell subclones instigate growth at distant sites of otherwise non-metastatic cancer cells. This is mediated systemically by perturbation in the metastatic tissue.

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.