Volume 24 Issue 8, August 2022

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.

NADPH levels serve as a biomarker of sensitivity to ferroptosis, but the regulators that detect cellular NADPH levels and modulate downstream ferroptosis responses are unknown. A study now identifies MARCHF6 in the ubiquitin system as an NADPH sensor that suppresses ferroptosis.

Aberrant subcellular localization of proteins contributes to the pathogenesis of cancer. A study now reports that the mis-localization of METTL3, a nuclear N⁶-adenosine methyltransferase, to the cytoplasm promotes gastric cancer by enhancing mRNA translation of a subset of oncogenes, independently of the N⁶-methyladenosine (m⁶A) modification.

EGFR is an oncogene that is frequently amplified in glioblastoma. A new study suggests a tumour-suppressive role of EGFR in EGFR-amplified glioblastoma regulated by ligand abundance. Increased EGFR ligand in EGFR-amplified glioblastoma suppresses invasion by upregulating BIN3 and inhibiting activation of Rho GTPases.

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.

Hao et al. describe an RNA-editing-independent role for ADAR1 in driving senescence. Autophagy downregulates ADAR1 in aged tissues, decreasing the binding of ADAR1 partner HuR to target mRNAs, including SIRT1. Loss of SIRT1 enhances p16^INK4a levels.

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.

Mylvaganam et al. report that an apical spectrin network in endothelial cells can transmit mechanical forces in response to shear flow-induced stress, requiring hyaluronic acid and involving PIEZO1.

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.

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.

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.

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.

Using single-cell analysis, Tan et al. map the cellular and spatial hierarchy and heterogeneity of eutopic endometrium and characterize ectopic peritoneal and ovarian endometriosis lesions from individuals receiving hormone treatment.