Reviews & Analysis

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  • Expansion of short tandem repeats can impair RNA and protein function and cause diseases through four main mechanisms: transcription repression, RNA gelation and sequestration of RNA-binding proteins, protein gain of function, and repeat-associated non-AUG toxic translation. Synergy between these mechanisms exacerbates disease, but also offers promising therapeutic targets.

    • Indranil Malik
    • Chase P. Kelley
    • Peter K. Todd
    Review Article
  • Liver regeneration involves multiple cell types, including hepatocytes, hepatic stellate cells, endothelial cells and inflammatory cells. Recent studies have elucidated the interactions between these cells during regeneration as well as the mechanisms that regulate cell proliferation and fibrosis remodelling, and have uncovered macrophages as key players. Such findings can help design novel therapeutic approaches.

    • Lara Campana
    • Hannah Esser
    • Stuart Forbes
    Review Article
  • The canonical function of endocytosis is molecule internalization. Beyond this role, endocytic trafficking has emerged as a process central to the spatiotemporal regulation of cell signalling. Endocytic trafficking thus controls many cellular processes and tissue-wide properties, including cell migration and polarity, and its deregulation has been implicated in pathologies, particularly cancer.

    • Sara Sigismund
    • Letizia Lanzetti
    • Pier Paolo Di Fiore
    Review Article
  • Cells can sense various signals, including chemical, mechanical, geometric and electrical signals, and migrate towards or away from them. Such directed cell migration involves signal generation, sensing and transduction that eventually lead to polarized force generation. Deciphering the mechanisms underlying these processes is crucial to understanding cell migration in vivo.

    • Shuvasree SenGupta
    • Carole A. Parent
    • James E. Bear
    Review Article
  • Recent technological breakthroughs in mapping and visualizing chromatin contacts have considerably improved our understanding of 3D genome organization and function. This Review discusses the features, strengths and limitations of various methods of genome organization analysis, including sequencing-based techniques, microscopy-based techniques and computational and modelling approaches.

    • Ivana Jerkovic´
    • Giacomo Cavalli
    Review Article
  • The cytoskeleton has been extensively implicated in regulating cell function and behaviour during development. This Review analyses the functional organization of cytoskeletal components in the early mouse embryo, and discusses key roles of the cytoskeleton during early mammalian embryogenesis, including regulation of cell fate specification and morphogenesis of the blastocyst.

    • Hui Yi Grace Lim
    • Nicolas Plachta
    Review Article
  • High-resolution imaging technologies have revealed that all living organisms localize mRNAs in subcellular compartments, creating translation hotspots that locally tune gene expression. Insight has been gained into the mechanisms of mRNA transport and local mRNA translation, including into the role of messenger ribonucleoproteins and higher-order RNA granules in these processes.

    • Sulagna Das
    • Maria Vera
    • Evelina Tutucci
    Review Article
  • Stromal progenitor cells contribute to the maintenance of tissue homeostasis in different organs. In vitro, these mesenchymal stromal cells (MSCs) can differentiate into many cell types. Recent omics and single-cell studies provide insights into the gene regulatory networks that drive lineage determination and cell differentiation, which has implications for the understanding of human diseases and for the development of cell-based therapies.

    • Alexander Rauch
    • Susanne Mandrup
    Review Article
  • MicroRNAs widely regulate systemic metabolism, prominently that of glucose and lipids. Consequently, microRNA misexpression can lead to metabolic diseases such as diabetes and atherosclerosis. MicroRNAs are therefore emerging as potential therapeutic targets to control metabolism and, owing to their secretion in extracellular vesicles, as metabolic biomarkers.

    • Pamela Agbu
    • Richard W. Carthew
    Review Article
  • Chromatin loops are proposed to be formed through loop extrusion by structural maintenance of chromosomes (SMC) complexes. Recent studies have shown that the SMC complexes condensin and cohesin are indeed able to extrude DNA, and caused a paradigm shift in our understanding of genome organization and the cellular functions of SMC complexes.

    • Iain F. Davidson
    • Jan-Michael Peters
    Review Article
  • Brown and beige adipocytes are mammalian thermogenic fat cells that regulate whole-body energy metabolism. Notably, brown/beige adipocytes are heterogeneous and their functions extend beyond thermogenesis, encompassing roles as metabolite sinks, as secretory cells and as regulators of adipose tissue homeostasis. Thus, induction of brown/beige fat activity correlates with improved metabolic health.

    • Paul Cohen
    • Shingo Kajimura
    Review Article
  • The histone modifiers Polycomb repressive complex 1 (PRC1) and PRC2 have important roles in development and disease, especially cancer. Recent studies have revealed the existence of various mutually exclusive PRC1 and PRC2 variants, and provided new insights into their molecular functions and physiological importance.

    • Andrea Piunti
    • Ali Shilatifard
    Review Article
  • Transfer RNAs (tRNAs) are heavily modified post-transcriptionally, and the number and types of modifications are continually expanding. Recent studies show that tRNA modifications can be altered in response to cellular and environmental stresses, and that deficiencies in tRNA modification can cause mitochondrial diseases, neurological disorders and cancer.

    • Tsutomu Suzuki
    Review Article
  • Direct reprogramming converts cells from one lineage into cells of another without going through an intermediary pluripotent state. This Review describes our current understanding of the molecular mechanisms underlying direct reprogramming as well as the progress in improving its efficiency and the maturation of reprogrammed cells, and the challenges associated with its translational applications.

    • Haofei Wang
    • Yuchen Yang
    • Li Qian
    Review Article
  • The majority of mitochondrial proteins are encoded in the nucleus, but mitochondria have an independent protein synthesis machinery that is required for the biogenesis of the respiratory chain. Recent insights into the mechanisms and regulation of mitochondrial protein synthesis have increased our understanding of mitochondrial function and its integration with cell physiology.

    • Eva Kummer
    • Nenad Ban
    Review Article
  • Biomolecular condensates, which form via liquid−liquid phase separation in a tightly regulated manner, have fundamental roles in cellular organization and physiology. Recent studies provide insight into how cellular stress, ageing-related loss of homeostasis and a decline in protein quality control may contribute to the formation of aberrant, disease-causing condensates.

    • Simon Alberti
    • Anthony A. Hyman
    Review Article
  • p38α — the best-characterized member of the p38 kinase family — is a key mediator of cellular stress responses. p38α is activated by a plethora of signals and functions through a multitude of substrates to regulate different cellular behaviours. Understanding context-dependent p38α signalling provides important insights into p38α roles in physiology and pathology.

    • Begoña Canovas
    • Angel R. Nebreda
    Review Article
  • Ferroptosis is a form of regulated cell death driven by iron-dependent phospholipid peroxidation. Since its formal identification in 2012, multiple studies have addressed molecular mechanisms, regulation and functions of ferroptosis, associating this cell death modality with various pathologies, but also proposing its roles in normal physiology and potential for therapeutic targeting.

    • Xuejun Jiang
    • Brent R. Stockwell
    • Marcus Conrad
    Review Article