Volume 26 Issue 2, February 2024

Sarah Teichmann, head of cellular genetics at the Wellcome Sanger Institute, reflects on the dawn of the single-cell genomics era and a pivotal decision that changed the course of her career.

Pietro De Camilli is a professor of neuroscience and of cell biology at Yale University, CT, as well as an investigator in the Howard Hughes Medical Institute. Pietro discusses how his group’s 1999 Nature Cell Biology study linking amphiphysin with dynamin in clathrin-mediated endocytosis came to be.

Maria Antonietta (Antonella) De Matteis is a professor of biology at the University of Naples Federico II and leads the cell biology programme at the Telethon Institute of Genetics and Medicine in Pozzuoli, Italy. Antonella recalls the beginning of her research program on phosphatidylinositol 4-phosphate (PI4P) at the Golgi, published in our pages in 1999 and 2004.

Danfeng Cai, an assistant professor in the Department of Biochemistry and Molecular Biology at the Johns Hopkins Bloomberg School of Public Health, discusses her career path, including her work on the biomolecular condensation of YAP, and her excitement in her ongoing work on transcriptional condensates.

Eiji Hara is a professor at the Research Institute for Microbial Diseases, Osaka University, Japan. Eiji recalls the discovery of the basis for the irreversibility of cellular senescence, published in Nature Cell Biology in 2006.

Despite a growing understanding of the immunostimulatory properties of mitochondrial DNA (mtDNA), little is known about how and why mtDNA escapes its mitochondrial confines. A study now describes an endosomal trafficking pathway that facilitates mtDNA egress and provides an additional mechanism of mtDNA release in vitro.

Lipids have a pivotal role in the growth of oocytes and fertilized eggs. Ultra-sensitive lipidome analysis provides a complete overview of the lipid profile during early embryonic development and brings insights into how dynamic lipid remodelling determines the fate of mammalian embryos.

van der Weijden et al. perform genomic, proteomic and metabolic analyses and find that FOXO1-mediated fatty acid oxidation maintains mouse embryos in diapause.

Newman et al. show that, upon mitochondrial DNA (mtDNA) replication stress, enlarged nucleoids are trafficked to endosomes. Endosomal rupture releases mtDNA into the cytoplasm, triggering cGAS–STING activation and innate immune signalling.

Villeneuve et al. report coordination of contractile forces during mammalian hair follicle development, with actomyosin contractility and mechanical forces from the epidermis and underlying tissue regulating placode invagination and Sox9 expression.

Wang, Chen et al. describe cGAS–STING pathway overactivation in neurons in models of lysosome storage disorders (LSDs). Inactivation of neuronal cGAS–STING signalling alleviates neurodegeneration, suggesting a unifying mechanism mediating LSD pathogenesis.

Son et al. show that AMPK- and PP2A-dependent p300 nucleocytoplasmic shuttling regulates mTORC1 activity in response to nutrient status. Models of Hutchinson–Gilford progeria syndrome display increased cytoplasmic p300 and mTORC1 hyperactivation.

Zwick et al. examine longitudinal transcriptional patterns across the entire mouse and human small intestine and find that, in both species, the small intestine comprises five domains of nutrient absorption and three regional stem cell populations.

Lin Li, Lei Li et al. perform single-cell multi-omics to study the transcriptome, the DNA methylome and chromatin accessibility in human arrested embryos and find that cytoskeletal defects cause embryonic arrest characterized by zygotic genome activation.

Using low-input lipidomics in mouse and human embryos, Zhang, Shui, Li and colleagues find that lipid unsaturation increases with development towards the blastocyst stage. They further show that lipid desaturases contribute to successful embryo implantation.

Huang, Qin, Shang et al. profile double-strand breaks (DSBs) generated by C-to-G base editors (CGBEs) and find that HMCES protects abasic sites and reduces CGBE-triggered DSBs.