In this Review, Polyak and colleagues discuss cellular and microenvironmental mechanisms that contribute to intratumour heterogeneity and how this affects immune escape and tumour progression.

Diehl et al. show that imbalance among nucleotide species is not sensed by canonical metabolic regulatory pathways, causing excessive cell growth despite a DNA replication block. ATR is needed to increase nucleotide availability in normal S phase.

Chandrakanthan et al. identify Mesp1-derived PDGFRA⁺ stromal cells as aortic endothelial precursors that regulate long-term haematopoietic-stem-cell generation during development, thus providing a new potential tool to generate engraftable haematopoietic stem cells.

Imaging technologies drive discovery in cell biology. Innovations in microscopy hardware, imaging methods and computational analysis of large-scale, complex datasets can increase imaging resolution, definition and allow access to new biology. We asked experts at the leading edge of biological imaging what they are most excited about when it comes to microscopy in cell biology and what challenges need to be overcome to reach these goals.

Nguyen et al. show that the E3 ubiquitin ligase MARCHF6 acts as an NADPH sensor to suppress ferroptosis. Mechanistically, NADPH binds to MARCHF6 and activates its E3 ligase activity, enhancing the degradation of pro-ferroptosis proteins.

Sahu et al. show that ZNF827 is essential for epithelial-to-mesenchymal transition in breast cancer metastasis and cortical development. Mechanistically, ZNF827 controls RNA splicing landscape by recruiting HDAC1 to slow RNA polymerase II progression.

Diehl et al. show that imbalance among nucleotide species is not sensed by canonical metabolic regulatory pathways, causing excessive cell growth despite a DNA replication block. ATR is needed to increase nucleotide availability in normal S phase.

Wei et al. identify that cytoplasmic METTL3 interacts with PABPC1 to facilitate translation of epigenetic factor mRNAs without m⁶A modification to promote tumour progression, suggesting an m⁶A-independent mechanism for this methyltransferase.

Guo et al. show that ligand-induced EGFR activation suppresses invasion by upregulating BIN3 and inhibiting DOCK7-regulated Rho GTPase activity in EGFR-amplified glioblastoma, which is in contrast to the known oncogenic role for EGFR signalling.

Chandrakanthan et al. identify Mesp1-derived PDGFRA⁺ stromal cells as aortic endothelial precursors that regulate long-term haematopoietic-stem-cell generation during development, thus providing a new potential tool to generate engraftable haematopoietic stem cells.

After earning a PhD in Molecular Systems Biology from ETH Zurich and studying cancer metabolism as a postdoctoral fellow at MIT, Sarah-Maria Fendt started an independent research group in 2013 in a joint appointment at the Flemish Institute for Biotechnology (VIB) and the University of Leuven (KU Leuven) in Belgium.

Pride holds a special place in the hearts of lesbian, gay, bisexual, transgender, queer, intersex, asexual+ (LGBTQIA+) individuals as a time to celebrate the progress we have made, and advocate for the advances yet to come. Here, I highlight ways in which the scientific community has had a crucial role in driving this progress, and provide a personal perspective on the importance of being open and proud of my identity as a gay cell biologist.