The transition of a pluripotent stem cell into a differentiated lineage is one of the most complex yet precisely orchestrated events in developmental biology. A study now reveals that mechanical and osmotic forces, long considered background players in guiding this transition, are essential regulators of chromatin accessibility and cell fate decisions.

McCreery, Stubb et al. show that mechano-osmotic changes in the nucleus induce general transcriptional repression and prime chromatin for cell fate transitions by relieving repression of specific differentiation genes.

The AMP-dependent protein kinase AMPK is thought to be activated only when cellular energy levels are low. However, a study now finds that intracellular AMP is generated from extracellular adenosine in an intricate growth signalling cascade, explaining how AMPK can be regulated by extracellular cues.

Zhang et al. demonstrate that AMPK can be activated by signalling metabolite, adenosine, under non-stress conditions during Drosophila development. The intestine regulates adenosine levels, thus, remotely controlling wing disc AMPK activation and growth.

Here the authors show that LC3-associated phagocytosis is initiated by various receptors, which enrich phosphatidylserine in the membrane domains proximal to the phagosome, recruiting Rubicon to the membrane for phagosome maturation.

Sun et al. identify a subset of transposable elements that serve as mechano-response enhancer elements that control gene expression and human stem cell fate.

Zhang, Lahry, Cipurko et al. show that the microbial metabolites queuine and preQ1 modify the same host tRNA. PreQ1-tRNA reduces cell proliferation, slows tumour growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER ribosome.

A study now indicates that CD160⁺CD8⁺ T cells in patients with colorectal cancer modulate anti-tumour immune responses and may influence disease progression. Their combination with immune checkpoint blockade therapy has emerged as a promising strategy to enhance therapeutic efficacy and patient outcomes in colorectal cancer.

Zheng et al. identify a role for CD160 in regulating CD8+ T cell exhaustion and cytotoxicity through the AKT–NF-κB pathway. The transfer of CD160+CD8+ T cells overcomes resistance to anti-PD-1 treatment in colorectal cancer models.

Al-Hilal, Chrysovergi et al. identify a role for durotaxis in lung fibrosis and metastatic pancreatic cancer, mediated by the FAK–paxillin mechanosensor complex, and demonstrate therapeutic targeting of this pathway using the small molecule JP-153.

During development as cells exit a pluripotent state, chromatin looping interactions are strengthened, but the mechanism for this is unknown. A study now shows that CTCF–RBP interactions increase upon differentiation of embryonic stem cells to neural stem cells, and that the non-coding RNA Pantr1 collaborates with CTCF and RBPs to contract the genome.

Djeghloul, Cheriyamkunnel et al. apply chromosome sorting to isolate active and inactive X chromosomes and report a role for Hbo1 and Msl histone acetyltransferase complexes in preserving active X chromosomes in female cells during mitosis.

Yin, Lin, Cai, Nie and colleagues report phase separation of ERCC6L2 as a mechanism that regulates RNF138-mediated ubiquitination and degradation of CtIP, thereby modulating DNA end resection and treatment response to ATM inhibitors in cancer.

Yang, Li, Huang, Ji, Luo, Jiang and colleagues report that chemotherapy induces MLKL PARylation and necroptosis in tumour endothelial cells, which in turn affects tumour-associated macrophages and CD8⁺ T cells, promoting immunosuppression and tumorigenesis.

Gasnier et al. identify NOX1 and NPY1R as markers of colon stem cells within the mouse caecum and the middle and distal colorectum, respectively. These stem cells contribute to the initiation of invas...

Xu et al. perform a whole-genome CRISPR-Cas9 knockout screen using directed differentiation systems. They find that MEN1 and SUZ12 modulate human developmental timing by epigenetically controlling biv...

Mauthe et al. find that protein aggregate clearance requires fragmentation of the aggregate by a chaperone module and a proteasomal regulatory particle for recruitment and clustering of selective auto...

Arabzade, Shirnekhi, Varadharajan, Ippagunta and colleagues show that the zinc finger translocation-associated (ZFTA) fusion oncoproteins gain intrinsically disordered regions, inducing nuclear conden...

This Perspective presents recent insights into vimentin filament structure and function and discusses emerging findings that point to a role in tumour invasion in mesenchymal cells analogous to embryo...